Amyloid Plaques
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Amyloid plaques (also known as neuritic plaques, amyloid beta plaques or senile plaques) are
extracellular This glossary of biology terms is a list of definitions of fundamental terms and concepts used in biology, the study of life and of living organisms. It is intended as introductory material for novices; for more specific and technical definitions ...
deposits of the
amyloid beta Amyloid beta (Aβ or Abeta) denotes peptides of 36–43 amino acids that are the main component of the amyloid plaques found in the brains of people with Alzheimer's disease. The peptides derive from the amyloid precursor protein (APP), which is ...
(Aβ)
protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
mainly in the
grey matter Grey matter is a major component of the central nervous system, consisting of neuronal cell bodies, neuropil (dendrites and unmyelinated axons), glial cells (astrocytes and oligodendrocytes), synapses, and capillaries. Grey matter is distingui ...
of the brain. Degenerative
neuron A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. N ...
al elements and an abundance of
microglia Microglia are a type of neuroglia (glial cell) located throughout the brain and spinal cord. Microglia account for about 7% of cells found within the brain. As the resident macrophage cells, they act as the first and main form of active immune de ...
and
astrocytes Astrocytes (from Ancient Greek , , "star" + , , "cavity", "cell"), also known collectively as astroglia, are characteristic star-shaped glial cells in the brain and spinal cord. They perform many functions, including biochemical control of endo ...
can be associated with amyloid plaques. Some plaques occur in the brain as a result of
aging Ageing ( BE) or aging ( AE) is the process of becoming older. The term refers mainly to humans, many other animals, and fungi, whereas for example, bacteria, perennial plants and some simple animals are potentially biologically immortal. In ...
, but large numbers of plaques and
neurofibrillary tangles Neurofibrillary tangles (NFTs) are aggregates of hyperphosphorylated tau protein that are most commonly known as a primary biomarker of Alzheimer's disease. Their presence is also found in numerous other diseases known as tauopathies. Little is k ...
are characteristic features of
Alzheimer's disease Alzheimer's disease (AD) is a neurodegeneration, neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in short-term me ...
. Abnormal
neurites A neurite or neuronal process refers to any projection from the cell body of a neuron. This projection can be either an axon or a dendrite. The term is frequently used when speaking of immature or developing neurons, especially of cells in culture, ...
in amyloid plaques are tortuous, often swollen
axon An axon (from Greek ἄξων ''áxōn'', axis), or nerve fiber (or nerve fibre: see spelling differences), is a long, slender projection of a nerve cell, or neuron, in vertebrates, that typically conducts electrical impulses known as action po ...
s and
dendrite Dendrites (from Greek δένδρον ''déndron'', "tree"), also dendrons, are branched protoplasmic extensions of a nerve cell that propagate the electrochemical stimulation received from other neural cells to the cell body, or soma, of the n ...
s. The neurites contain a variety of
organelles In cell biology, an organelle is a specialized subunit, usually within a cell, that has a specific function. The name ''organelle'' comes from the idea that these structures are parts of cells, as organs are to the body, hence ''organelle,'' the ...
and cellular debris, and many of them include characteristic paired helical filaments, the
ultrastructural Ultrastructure (or ultra-structure) is the architecture of cells and biomaterials that is visible at higher magnifications than found on a standard optical light microscope. This traditionally meant the resolution and magnification range of a co ...
component of neurofibrillary tangles. The plaques are highly variable in shape and size; in tissue sections immunostained for Aβ, they comprise a
log-normal In probability theory, a log-normal (or lognormal) distribution is a continuous probability distribution of a random variable whose logarithm is normally distributed. Thus, if the random variable is log-normally distributed, then has a normal ...
size distribution curve with an average plaque area of 400-450 square
micrometers The micrometre (American and British English spelling differences#-re, -er, international spelling as used by the International Bureau of Weights and Measures; SI symbol: μm) or micrometer (American and British English spelling differences# ...
(µm²). The smallest plaques (less than 200 µm²), which often consist of diffuse deposits of Aβ, are particularly numerous. The apparent size of plaques is influenced by the type of stain used to detect them, and by the plane through which they are sectioned for analysis under the microscope. Plaques form when Aβ
misfold Protein folding is the physical process by which a protein chain is translated to its native three-dimensional structure, typically a "folded" conformation by which the protein becomes biologically functional. Via an expeditious and reproduci ...
s and aggregates into
oligomers In chemistry and biochemistry, an oligomer () is a molecule that consists of a few repeating units which could be derived, actually or conceptually, from smaller molecules, monomers.Quote: ''Oligomer molecule: A molecule of intermediate relative ...
and longer
polymers A polymer (; Greek '' poly-'', "many" + ''-mer'', "part") is a substance or material consisting of very large molecules called macromolecules, composed of many repeating subunits. Due to their broad spectrum of properties, both synthetic an ...
, the latter of which are characteristic of
amyloid Amyloids are aggregates of proteins characterised by a Fibril, fibrillar morphology of 7–13 Nanometer, nm in diameter, a beta sheet (β-sheet) Secondary structure of proteins, secondary structure (known as cross-β) and ability to be Staining, ...
. Misfolded and aggregated Aβ is thought to be
neurotoxic Neurotoxicity is a form of toxicity in which a biological, chemical, or physical agent produces an adverse effect on the structure or function of the central and/or peripheral nervous system. It occurs when exposure to a substance – specificall ...
, especially in its oligomeric state.


History

In 1892, Paul Blocq and
Gheorghe Marinescu Gheorghe Marinescu (; 28 February 1863 – 15 May 1938) was a Romanian neurologist, founder of the Romanian School of Neurology. History After attending the Faculty of Medicine of the University of Bucharest, Marinescu received most of his medi ...
first described the presence of plaques in grey matter. They referred to the plaques as 'nodules of neuroglial sclerosis'. In 1898, Emil Redlich reported plaques in three patients, two of whom had clinically verified
dementia Dementia is a disorder which manifests as a set of related symptoms, which usually surfaces when the brain is damaged by injury or disease. The symptoms involve progressive impairments in memory, thinking, and behavior, which negatively affe ...
. Redlich used the term 'miliary sclerosis' to describe plaques because he thought they resembled millet seeds, and he was the first to refer to the
lesion A lesion is any damage or abnormal change in the tissue of an organism, usually caused by disease or trauma. ''Lesion'' is derived from the Latin "injury". Lesions may occur in plants as well as animals. Types There is no designated classifi ...
s as 'plaques'. In the early 20th century,
Oskar Fischer Oskar Fischer (12 April 1876 – 28 February 1942) was a Czech academic, psychiatrist and neuropathologist whose studies on dementia and Alzheimer disease were rediscovered in 2008. Early life and education Fischer was born into a German-s ...
noted their similarity to
actinomyces ''Actinomyces'' is a genus of the Actinomycetia class of bacteria. They all are gram-positive. ''Actinomyces'' species are facultatively anaerobic and they grow best under anaerobic conditions. ''Actinomyces'' species may form endospores, an ...
'Drusen' (geode-like lesions), leading him to call the degenerative process 'drusige Nekrose'.
Alois Alzheimer Alois Alzheimer ( , , ; 14 June 1864 – 19 December 1915) was a German psychiatrist and neuropathologist and a colleague of Emil Kraepelin. Alzheimer is credited with identifying the first published case of "presenile dementia", which Kraepel ...
is often credited with first linking plaques to dementia in a 1906 presentation (published in 1907), but this short report focused mainly on neurofibrillary tangles, and plaques were only briefly mentioned. Alzheimer's first substantive description of plaques appeared in 1911. In contrast, Oskar Fischer published a series of comprehensive investigations of plaques and dementia in 1907, 1910 and 1912. By 1911
Max Bielschowsky Max Israel Bielschowsky (20 February 1869 – 15 August 1940) was a German neuropathologist born in Breslau. After receiving his medical doctorate from the University of Munich in 1893, he worked with Ludwig Edinger (1855–1918) at the ...
proposed the amyloid-nature of plaque deposits. This was later confirmed by Paul Divry, who showed that plaques that are stained with the dye
Congo Red Congo red is an organic compound, the sodium salt of 3,3′-( ,1′-biphenyl4,4′-diyl)bis(4-aminonaphthalene-1-sulfonic acid). It is an azo dye. Congo red is water-soluble, yielding a red colloidal solution; its solubility is greater in organic ...
show the optical property of
birefringence Birefringence is the optical property of a material having a refractive index that depends on the polarization and propagation direction of light. These optically anisotropic materials are said to be birefringent (or birefractive). The birefring ...
, which is characteristic of amyloids in general. In 1911,
Teofil Simchowicz Teofil Simchowicz (3 June 1879 – 31 December 1957) was a Polish neurologist who was born in Ciechanowiec near Warsaw, Poland. He studied medicine at the Imperial University of Warsaw, and received a medical degree in 1905. In years 1907-1910 he ...
introduced the term 'senile plaques' to denote their frequent presence in the brains of older individuals. In 1968, a quantitative analysis by Gary Blessed, Bernard Tomlinson and Martin Roth confirmed the association of senile plaques with
dementia Dementia is a disorder which manifests as a set of related symptoms, which usually surfaces when the brain is damaged by injury or disease. The symptoms involve progressive impairments in memory, thinking, and behavior, which negatively affe ...
. Henryk Wisniewski and Robert Terry coined the term 'neuritic plaques' in 1973 to designate plaques that include abnormal neuronal processes (neurites). An important advance in 1984 and 1985 was the identification of Aβ as the protein that forms the cores of plaques. This discovery led to the generation of new tools to study plaques, particularly antibodies to Aβ, and presented a molecular target for the development of potential therapies for Alzheimer's disease. Knowledge of the
amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...
sequence of Aβ also enabled scientists to discover genetic mutations that cause
autosomal dominant In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...
Alzheimer's disease, all of which increase the likelihood that Aβ will aggregate in the brain.


The generation of amyloid beta

Amyloid beta (Aβ) is a small protein, most often 40 or 42 amino acids in length, that is released from a longer parent protein called the Aβ-precursor protein (APP). APP is produced by many types of cell in the body, but it is especially abundant in
neuron A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. N ...
s. It is a single-pass
transmembrane protein A transmembrane protein (TP) is a type of integral membrane protein that spans the entirety of the cell membrane. Many transmembrane proteins function as gateways to permit the transport of specific substances across the membrane. They frequentl ...
, passing once through cellular
membrane A membrane is a selective barrier; it allows some things to pass through but stops others. Such things may be molecules, ions, or other small particles. Membranes can be generally classified into synthetic membranes and biological membranes. B ...
s. The Aβ segment of APP is partly within the membrane and partly outside of the membrane. To liberate Aβ, APP is sequentially cleaved by two
enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...
s: first, by
beta secretase Beta-secretase 1, also known as beta-site amyloid precursor protein cleaving enzyme 1, beta-site APP cleaving enzyme 1 (BACE1), membrane-associated aspartic protease 2, memapsin-2, aspartyl protease 2, and ASP2, is an enzyme that in humans is enco ...
(or β-amyloid cleaving enzyme (BACE)) outside the membrane, and second, by
gamma secretase Gamma secretase is a multi-subunit protease complex, itself an integral membrane protein, that cleaves single-pass transmembrane proteins at residues within the transmembrane domain. Proteases of this type are known as intramembrane proteases. Th ...
(γ-secretase), an enzyme complex within the membrane. The sequential actions of these secretases results in Aβ protein fragments that are released into the extracellular space The discharge of Aβ is increased by the activity of
synapse In the nervous system, a synapse is a structure that permits a neuron (or nerve cell) to pass an electrical or chemical signal to another neuron or to the target effector cell. Synapses are essential to the transmission of nervous impulses from ...
s. In addition to Aβ peptides that are 40 or 42 amino acids long, several less abundant Aβ fragments also are generated. Aβ can be chemically modified in various ways, and the length of the protein and chemical modifications can influence both its tendency to aggregate and its toxicity.


Identification

Amyloid plaques are visible with the
light microscope The optical microscope, also referred to as a light microscope, is a type of microscope that commonly uses visible light and a system of lenses to generate magnified images of small objects. Optical microscopes are the oldest design of microsco ...
using a variety of staining techniques, including
silver stain In pathology, silver staining is the use of silver to selectively alter the appearance of a target in microscopy of histological sections; in temperature gradient gel electrophoresis; and in polyacrylamide gels. In traditional stained glass, silv ...
s,
Congo red Congo red is an organic compound, the sodium salt of 3,3′-( ,1′-biphenyl4,4′-diyl)bis(4-aminonaphthalene-1-sulfonic acid). It is an azo dye. Congo red is water-soluble, yielding a red colloidal solution; its solubility is greater in organic ...
,
Thioflavin Thioflavins are fluorescent dyes that are available as at least two compounds, namely Thioflavin T and Thioflavin S. Both are used for histology staining and biophysics, biophysical studies of protein aggregation. In particular, these dyes have be ...
,
cresyl violet Cresyl violet is an organic Chemical compound, compound with the chemical formula C19H18ClN3O. It is a basic dye and is used as a common staining, stain in histology. Cresyl violet stain It is used in biology and medicine as a histology, histo ...
, PAS-reaction, and luminescent conjugated oligothiophenes (LCOs). These methods often stain different components of the plaques, and they vary in their sensitivity Plaques may also be visualized immunohistochemically with antibodies directed against Aβ or other components of the lesions. Immunohistochemical stains are especially useful because they are both sensitive and specific for
antigens In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. ...
that are associated with plaques.


Composition

The Aβ deposits that comprise amyloid plaques are variable in size and appearance. Under the light microscope, they range from small, wispy accumulations that are a few
micron The micrometre ( international spelling as used by the International Bureau of Weights and Measures; SI symbol: μm) or micrometer (American spelling), also commonly known as a micron, is a unit of length in the International System of Unit ...
s in diameter to much larger dense or diffuse masses. So-called 'classical plaques' consist of a compact Aβ-amyloid core that is surrounded by a corona of somewhat less densely packed Aβ. Classical plaques also include abnormal, swollen neuronal processes (
neurite A neurite or neuronal process refers to any projection from the cell body of a neuron. This projection can be either an axon or a dendrite. The term is frequently used when speaking of immature or developing neurons, especially of cells in culture ...
s) deriving from many different types of neurons, along with activated
astrocyte Astrocytes (from Ancient Greek , , "star" + , , "cavity", "cell"), also known collectively as astroglia, are characteristic star-shaped glial cells in the brain and spinal cord. They perform many functions, including biochemical control of endo ...
s and
microglia Microglia are a type of neuroglia (glial cell) located throughout the brain and spinal cord. Microglia account for about 7% of cells found within the brain. As the resident macrophage cells, they act as the first and main form of active immune de ...
. Abnormal neurites and activated
glial cells Glia, also called glial cells (gliocytes) or neuroglia, are non-neuronal cells in the central nervous system (brain and spinal cord) and the peripheral nervous system that do not produce electrical impulses. They maintain homeostasis, form mye ...
are not typical of most diffuse plaques, and it has been suggested that diffuse deposits are an early stage in the development of plaques.


Anatomical distribution

Dietmar Thal and his colleagues have proposed a sequence of stages of plaque formation in the brains of Alzheimer patients In Phase 1, plaques appear in the
neocortex The neocortex, also called the neopallium, isocortex, or the six-layered cortex, is a set of layers of the mammalian cerebral cortex involved in higher-order brain functions such as sensory perception, cognition, generation of motor commands, sp ...
; in Phase 2, they appear in the
allocortex The allocortex or heterogenetic cortex, and neocortex are the two types of cerebral cortex in the brain. The allocortex is the much smaller area of cortex taking up just 10 %, the neocortex takes up the remaining 90 %. It is characterized by havi ...
,
hippocampal formation The hippocampal formation is a compound structure in the Temporal lobe#Medial temporal lobe, medial temporal lobe of the brain. It forms a c-shaped bulge on the floor of the temporal horn of the Lateral ventricles, lateral ventricle. There is no ...
and
amygdala The amygdala (; plural: amygdalae or amygdalas; also '; Latin from Greek, , ', 'almond', 'tonsil') is one of two almond-shaped clusters of nuclei located deep and medially within the temporal lobes of the brain's cerebrum in complex verteb ...
; in Phase 3, the
basal ganglia The basal ganglia (BG), or basal nuclei, are a group of subcortical nuclei, of varied origin, in the brains of vertebrates. In humans, and some primates, there are some differences, mainly in the division of the globus pallidus into an extern ...
and
diencephalon The diencephalon (or interbrain) is a division of the forebrain (embryonic ''prosencephalon''). It is situated between the telencephalon and the midbrain (embryonic ''mesencephalon''). The diencephalon has also been known as the 'tweenbrain in ol ...
are affected; in Phase 4, plaques appear in the
midbrain The midbrain or mesencephalon is the forward-most portion of the brainstem and is associated with vision, hearing, motor control, sleep and wakefulness, arousal (alertness), and temperature regulation. The name comes from the Greek ''mesos'', " ...
and
medulla oblongata The medulla oblongata or simply medulla is a long stem-like structure which makes up the lower part of the brainstem. It is anterior and partially inferior to the cerebellum. It is a cone-shaped neuronal mass responsible for autonomic (involun ...
; and in Phase 5, they appear in the
pons The pons (from Latin , "bridge") is part of the brainstem that in humans and other bipeds lies inferior to the midbrain, superior to the medulla oblongata and anterior to the cerebellum. The pons is also called the pons Varolii ("bridge of Va ...
and
cerebellum The cerebellum (Latin for "little brain") is a major feature of the hindbrain of all vertebrates. Although usually smaller than the cerebrum, in some animals such as the mormyrid fishes it may be as large as or even larger. In humans, the cerebel ...
. Thus, in end-stage Alzheimer's disease, plaques can be found in most parts of the brain. They are uncommon in the
spinal cord The spinal cord is a long, thin, tubular structure made up of nervous tissue, which extends from the medulla oblongata in the brainstem to the lumbar region of the vertebral column (backbone). The backbone encloses the central canal of the spi ...
.


Formation and spread

The normal function of Aβ is not certain, but plaques arise when the protein misfolds and begins to accumulate in the brain by a process of molecular templating ('seeding'). Mathias Jucker and
Lary Walker Lary Walker is an American neuroscientist and researcher at Emory University in Atlanta, Georgia. He is Associate Director of the Goizueta Alzheimer's Disease Research Center at Emory, and he is known for his research on the role of abnormal pr ...
have likened this process to the formation and spread of
prion Prions are misfolded proteins that have the ability to transmit their misfolded shape onto normal variants of the same protein. They characterize several fatal and transmissible neurodegenerative diseases in humans and many other animals. It ...
s in diseases known as spongiform encephalopathies or
prion diseases Prions are Proteinopathy, misfolded proteins that have the ability to transmit their misfolded shape onto normal variants of the same protein. They characterize several fatal and transmissible neurodegenerative diseases in humans and many othe ...
. According to the prion paradigm, certain proteins misfold into shapes that are rich in
beta-sheet The beta sheet, (β-sheet) (also β-pleated sheet) is a common motif of the regular protein secondary structure. Beta sheets consist of beta strands (β-strands) connected laterally by at least two or three backbone hydrogen bonds, forming a g ...
secondary structure Protein secondary structure is the three dimensional conformational isomerism, form of ''local segments'' of proteins. The two most common Protein structure#Secondary structure, secondary structural elements are alpha helix, alpha helices and beta ...
. In this state, they cause other proteins of the same type to adopt the same abnormal beta-sheet-rich structure. The misfolded proteins stick to one another, eventually stacking together to form
oligomer In chemistry and biochemistry, an oligomer () is a molecule that consists of a few repeating units which could be derived, actually or conceptually, from smaller molecules, monomers.Quote: ''Oligomer molecule: A molecule of intermediate relativ ...
s that merge to make the amyloid fibrils that are typical of mature plaques.


Involvement in disease

Abundant Aβ plaques, along with
neurofibrillary tangles Neurofibrillary tangles (NFTs) are aggregates of hyperphosphorylated tau protein that are most commonly known as a primary biomarker of Alzheimer's disease. Their presence is also found in numerous other diseases known as tauopathies. Little is k ...
consisting of aggregated
tau protein The tau proteins (abbreviated from tubulin associated unit) are a group of six highly soluble protein isoforms produced by alternative splicing from the gene ''MAPT'' (microtubule-associated protein tau). They have roles primarily in maintaining ...
, are the two lesions that are required for the neuropathological diagnosis of Alzheimer's disease. Although the number of neurofibrillary tangles correlates more strongly with the degree of dementia than does the number of plaques, genetic and pathologic findings indicate that Aβ plays a central role in the risk, onset, and progression of Alzheimer's disease. Of particular importance is the longer (42 amino acids) species of Aβ known as Aβ42. Elevated levels of Aβ, as well as an increase in the ratio of Aβ42 to the 40-amino acid form (Aβ40), are important early events in the pathogenesis of Alzheimer's disease. Until recently, the diagnosis of Alzheimer's disease required a microscopic analysis of plaques and tangles in brain tissue, usually at autopsy. However, Aβ plaques (along with cerebral Aβ-amyloid angiopathy) can now be detected in the brains of living subjects. This is done by preparing
radiolabeled A radioactive tracer, radiotracer, or radioactive label is a chemical compound in which one or more atoms have been replaced by a radionuclide so by virtue of its radioactive decay it can be used to explore the mechanism of chemical reactions by tr ...
agents that bind selectively to Aβ deposits in the brain after being infused into the bloodstream. The
ligand In coordination chemistry, a ligand is an ion or molecule (functional group) that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's electr ...
s cross the
blood–brain barrier The blood–brain barrier (BBB) is a highly selective semipermeable membrane, semipermeable border of endothelium, endothelial cells that prevents solutes in the circulating blood from ''non-selectively'' crossing into the extracellular fluid of ...
and attach to aggregated Aβ, and their retention in the brain is assessed by
positron emission tomography Positron emission tomography (PET) is a functional imaging technique that uses radioactive substances known as radiotracers to visualize and measure changes in Metabolism, metabolic processes, and in other physiological activities including bl ...
(PET). In addition, the presence of plaques and tangles can be estimated by measuring the amounts of the Aβ and tau proteins in the
cerebrospinal fluid Cerebrospinal fluid (CSF) is a clear, colorless body fluid found within the tissue that surrounds the brain and spinal cord of all vertebrates. CSF is produced by specialised ependymal cells in the choroid plexus of the ventricles of the bra ...
.


Occurrence

The probability of having plaques in the brain increases with advancing age. From the age of 60 years (10%) to the age of 80 years (60%), the proportion of people with senile plaques increases linearly. Women are slightly more likely to have plaques than are men. Both plaques and Alzheimer's disease also are more common in aging persons with
trisomy A trisomy is a type of polysomy in which there are three instances of a particular chromosome, instead of the normal two. A trisomy is a type of aneuploidy (an abnormal number of chromosomes). Description and causes Most organisms that reprodu ...
-21 (
Down syndrome Down syndrome or Down's syndrome, also known as trisomy 21, is a genetic disorder caused by the presence of all or part of a third copy of chromosome 21. It is usually associated with physical growth delays, mild to moderate intellectual dis ...
). This is thought to result from the excess production of Aβ because the ''APP'' gene is on chromosome 21, which exists as three copies in Down syndrome. Amyloid plaques naturally occur in the aging brains of nonhuman species ranging from birds to great apes. In nonhuman primates, which are the closest biological relatives of humans, plaques have been found in all species examined thus far. Neurofibrillary tangles are rare, however, and no nonhuman species has been shown to have dementia along with the complete neuropathology of Alzheimer's disease.


Research

Research using human samples and
experimental models of Alzheimer's disease Experimental models of Alzheimer's disease are organism or cellular models used in research to investigate biological questions about Alzheimer's disease as well as develop and test novel therapeutic treatments. Alzheimer's disease is a progressive ...
has been directed toward understanding the
biochemical Biochemistry or biological chemistry is the study of chemical processes within and relating to living organisms. A sub-discipline of both chemistry and biology, biochemistry may be divided into three fields: structural biology, enzymology an ...
,
cytological Cell biology (also cellular biology or cytology) is a branch of biology that studies the structure, function, and behavior of cells. All living organisms are made of cells. A cell is the basic unit of life that is responsible for the living and ...
, and inflammatory characteristics of plaques, determining how plaques arise and proliferate in the brain, identifying genetic and environmental risk factors, discovering methods to detect them in the living brain, and developing therapeutic strategies for preventing or removing them. Amyloid plaque formation may be linked to hemorrhage from brain
microvessels The microcirculation is the circulation of the blood in the smallest blood vessels, the microvessels of the microvasculature present within organ tissues. The microvessels include terminal arterioles, metarterioles, capillaries, and venules. ...
. Research on the formation and proliferation of amyloid plaques has been accelerated by the development of
genetically modified Genetic engineering, also called genetic modification or genetic manipulation, is the modification and manipulation of an organism's genes using technology. It is a set of Genetic engineering techniques, technologies used to change the gene ...
mouse models. Numerous candidate treatments that reduce Aβ levels and the number of plaques in the brain have been identified with the help of
transgenic A transgene is a gene that has been transferred naturally, or by any of a number of genetic engineering techniques, from one organism to another. The introduction of a transgene, in a process known as transgenesis, has the potential to change the ...
rodent models. These strategies include immunotherapeutic approaches and inhibitors of the secretases that release Aβ from APP. Earlier inhibition of Aβ aggregation and plaque formation may be needed to slow or prevent
tauopathy Tauopathy belongs to a class of neurodegenerative diseases involving the aggregation of tau protein into neurofibrillary or gliofibrillary tangles in the human brain. Tangles are formed by hyperphosphorylation of the microtubule protein known a ...
and Alzheimer's disease. Other research is directed toward understanding the inflammation associated with plaques and identifying environmental, physiological or genetic risk factors for plaque formation in Alzheimer's disease.


See also

*
Proteopathy In medicine, proteinopathy (; 'pref''. protein -pathy 'suff''. disease proteinopathies ''pl''.; proteinopathic ''adj''), or proteopathy, protein conformational disorder, or protein misfolding disease refers to a class of diseases in which certa ...


References


Further reading

* *{{cite journal , vauthors=Cruz L, Urbanc B, Buldyrev SV, etal , title=Aggregation and disaggregation of senile plaques in Alzheimer disease , journal=Proceedings of the National Academy of Sciences of the United States of America , volume=94 , issue=14 , pages=7612–6 , date=July 1997 , pmid=9207140 , pmc=23870 , doi=10.1073/pnas.94.14.7612, bibcode=1997PNAS...94.7612C , doi-access=free Histopathology