Lary Walker is an American

neuroscientist A neuroscientist (or neurobiologist) is a scientist who has specialised knowledge in neuroscience, a branch of biology that deals with the physiology, biochemistry, psychology, anatomy and molecular biology of neurons, Biological neural network, n ...

and researcher at

Emory University Emory University is a private research university in Atlanta, Georgia. Founded in 1836 as "Emory College" by the Methodist Episcopal Church and named in honor of Methodist bishop John Emory, Emory is the second-oldest private institution of ...

Atlanta, Georgia Atlanta ( ) is the capital and most populous city of the U.S. state of Georgia. It is the seat of Fulton County, the most populous county in Georgia, but its territory falls in both Fulton and DeKalb counties. With a population of 498,715 ...

. 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 proteins in the causation of

Alzheimer’s disease Alzheimer's disease (AD) is a 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 remembering recent events. As t ...

Education and career

Walker received his Bachelor of Science degree from

Louisiana State University Louisiana State University (officially Louisiana State University and Agricultural and Mechanical College, commonly referred to as LSU) is a public land-grant research university in Baton Rouge, Louisiana. The university was founded in 1860 nea ...

, and his Master of Science and PhD degrees from

Tulane University Tulane University, officially the Tulane University of Louisiana, is a private university, private research university in New Orleans, Louisiana. Founded as the Medical College of Louisiana in 1834 by seven young medical doctors, it turned into ...

. Following a German Academic Exchange (DAAD) Fellowship at the

University of Kassel The University of Kassel (german: link=no, Universität Kassel) is a university founded in 1971 located in Kassel, Hessen, in central Germany. As of February 2022 it had about 25,000 students and about 3300 staff, including more than 300 prof ...

and a

National Institutes of Health The National Institutes of Health, commonly referred to as NIH (with each letter pronounced individually), is the primary agency of the United States government responsible for biomedical and public health research. It was founded in the late ...

(NIH) postdoctoral fellowship at Emory University, he moved to the Neuropathology Laboratory of Donald L. Price at

Johns Hopkins University Johns Hopkins University (Johns Hopkins, Hopkins, or JHU) is a private university, private research university in Baltimore, Maryland. Founded in 1876, Johns Hopkins is the oldest research university in the United States and in the western hem ...

, where he began work on the biological basis of Alzheimer's disease. In 1995 he became head of the Alzheimer's disease drug discovery program at Parke-Davis/Warner-Lambert in

Ann Arbor, Michigan Ann Arbor is a city in the U.S. state of Michigan and the county seat of Washtenaw County, Michigan, Washtenaw County. The 2020 United States census, 2020 census recorded its population to be 123,851. It is the principal city of the Ann Arbor ...

. In 2003 he returned to Emory University, where he is the Marie and E.R. Snelling Professor of Neurology.

Research

Biology of Aβ (senile) plaques

Walker's early research established that a variety of neurons are involved in the formation of Aβ plaques, one of the pathological hallmarks of Alzheimer's disease. With Dale Schenk at Athena Neurosciences (later part of

Élan Elan Corporation plc was a major drugs firm based in Dublin, Ireland, which had major interests in the United States. It was listed on the New York Stock Exchange as ELN, the Irish Stock Exchange as ELN.I, and the London Stock Exchange as ELN. ...

Pharmaceuticals), he discovered that antibodies to the

Aβ 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 ...

protein can enter the brain from 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 ...

and selectively bind to Aβ plaques and cerebral Aβ-amyloid angiopathy (CAA). Based on his work with

animal models A model organism (often shortened to model) is a non-human species that is extensively studied to understand particular biological phenomena, with the expectation that discoveries made in the model organism will provide insight into the working ...

of Alzheimer's disease, Walker has proposed that humans are uniquely vulnerable to Alzheimer's disease.

Prion-like properties of disease-causing proteins

Since the late 1990s, Walker's research has been directed toward the mechanisms that drive the misfolding and aggregation of the Aβ protein in the living brain. In collaboration with Mathias Jucker at the

University of Tübingen The University of Tübingen, officially the Eberhard Karl University of Tübingen (german: Eberhard Karls Universität Tübingen; la, Universitas Eberhardina Carolina), is a public research university located in the city of Tübingen, Baden-Wü ...

, he discovered that the accumulation of Aβ can be initiated in

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 ...

mouse models by a

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 ...

-like mechanism in which 'seeds' of abnormal Aβ precipitate the formation of plaques and CAA. In 2000, Walker and Harry LeVine introduced the term '

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 ...

' (also known as 'proteinopathy') to describe diseases characterized by the misfolding and aggregation of proteins. This terminology has been applied to a number of neurodegenerative disorders and amyloidoses, including tauopathies such as

Pick's disease Frontotemporal dementia (FTD), or frontotemporal degeneration disease, or frontotemporal neurocognitive disorder, encompasses several types of dementia involving the progressive degeneration of frontal and temporal lobes. FTDs broadly present as ...

, synucleinopathies such as

Parkinson's disease Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms becom ...

and

Lewy Body Dementia Lewy body dementias are two similar and common subtypes of dementia—dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD). Both are characterized by changes in thinking, movement, behavior, and mood. The two conditions have sim ...

systemic Systemic fundamental to a predominant social, economic, or political practice. This refers to: In medicine In medicine, ''systemic'' means affecting the whole body, or at least multiple organ systems. It is in contrast with ''topical'' or ''loc ...

amyloidoses, and others.

Awards

Walker received the

Metlife Foundation Award for Medical Research in Alzheimer's Disease The Metlife Foundation Award for Medical Research in Alzheimer's Disease were awarded annually from 1986 to 2016 to recognize scientific contributions toward a better understanding of the underlying causes, prevention, and treatments of Alzheimer's ...

in 2014, the

Alexander von Humboldt Research Award The Humboldt Prize, the Humboldt-Forschungspreis in German, also known as the Humboldt Research Award, is an award given by the Alexander von Humboldt Foundation of Germany to internationally renowned scientists and scholars who work outside of G ...

in 2016, and the Peter Bassoe Lectureship of the

American Neuropsychiatric Association The American Neuropsychiatric Association (ANPA) is a non-profit organization of professionals in neuropsychiatry, behavioral neurology and the clinical neurosciences, with over 700 members from around the world. Established in 1988, its mission ...

in 2017.

Bibliography

Selected reviews

* “Seeds of Dementia”. Walker LC and Jucker M (2013). ''Scientific American'' 308: 52-57. PMID: 23627220. https://DOI:10.1038/scientificamerican0513-52. * “Mechanisms of protein seeding in neurodegenerative diseases” Walker LC, Diamond MI, Duff KE and Hyman BT (2013). ''JAMA Neurology'' 70: 304-310. PMID: 23599928. PMCID: PMC3665718. https://DOI:10.1001/jamaneurol.2013.1453. * “Self-propagation of pathogenic protein aggregates in neurodegenerative diseases”. Jucker M and Walker LC (2013). ''Nature'' 501: 45-51. PMID: 24005412. PMCID: PMC3963807. https://DOI:10.1038/nature12481. * “Neurodegenerative diseases: Expanding the prion concept”. Walker LC and Jucker M (2015). ''Annual Review of Neuroscience'' 38: 87-103. PMID: 25840008. PMCID: PMC4803040. https://DOI:10.1146/annurev-neuro-071714-033828. * “Proteopathic strains and the heterogeneity of neurodegenerative diseases”. Walker LC (2016). ''Annual Review of Genetics'' 50: 329-346. PMID: 27893962. PMCID: PMC6690197. https://DOI:10.1146/annurev-genet-120215-034943. * “Propagation and spread of pathogenic protein assemblies in neurodegenerative diseases”. Jucker M, Walker LC (2018). ''Nature Neuroscience'' 21: 1341-1349. PMID: 30258241. PMCID: PMC6375686. https://DOI:10.1038/s41593-018-0238-6.

Selected research reports

* “Augmented senile plaque load in aged female β-amyloid precursor protein transgenic mice”. Callahan MJ, Lipinski WJ, Bian F, Durham RA, Pack A and Walker LC (2001). ''American Journal of Pathology'' 158: 1173-1177. PMID: 11238065. PMCID: PMC1850367. https://DOI:10.1016/s0002-9440(10)64064-3. * “Exogenous induction of Aβ-amyloidogenesis is governed by intrinsic properties of agent and host”. Meyer-Luehmann M, Coomaraswamy J, Bolmont T, Kaeser S, Schaefer C, Kilger E, Neuenschwander A, Abramowski D, Frey P, Jaton AL, Vigouret J, Paganetti P, Walsh DM, Mathews P, Ghiso J, Staufenbiel M, Walker LC and Jucker M (2006). ''Science'' 313: 1781-1784. PMID: 16990547. https://DOI:10.1126/science.1131864. * “Deficient high-affinity binding of Pittsburgh Compound B in a case of Alzheimer's disease”. Rosen RF, Ciliax BJ, Gearing M, Dooyema J, Wingo T, Lah JJ, Ghiso JA, LeVine III H and Walker LC (2010). ''Acta Neuropathologica'' 119: 221-233. PMID: 19690877. PMCID: PMC3045810. https://DOI:10.1007/s00401-009-0583-3. * “Exogenous seeding of cerebral β-amyloid deposition in βAPP-transgenic rats”. Rosen RF, Fritz JJ, Dooyema J, Cintron AF, Hamaguchi T, Lah JJ, LeVine III H, Jucker M and Walker LC (2012). ''Journal of Neurochemistry'' 120: 660-666. PMID: 22017494. PMCID: PMC3293176. https://DOI:10.1111/j.1471-4159.2011.07551.x. * “Amyloid polymorphisms constitute distinct clouds of conformational variants in different etiological subtypes of Alzheimer's disease”. Rasmussen J, Mahler J, Beschorner N, Kaeser SA, Häsler LM, Baumann F, Nyström S, Portelius E, Blennow K, Lashley T, Fox NC, Sepulveda-Falla D, Glatzel M, Oblak AL, Ghetti B, Nilsson KPR, Hammarström P, Staufenbiel M, Walker LC and Jucker M (2017). ''Proceedings of the National Academy of Sciences USA'' 114: 13018-13023. PMID: 29158413. PMCID: PMC5724274. https://DOI:10.1073/pnas.1713215114.

Complete list of published work

* https://scholar.google.com/citations?user=Ap8lgXEAAAAJ&hl=en&oi=sra * http://www.ncbi.nlm.nih.gov/sites/myncbi/1feivrkCu97Q5/bibliography/41295477/public/?sort=date&direction=descending

Selected book chapters

* “The neurobiology of aging in nonhuman primates”. Walker LC and Cork LC (1999). In: ''Alzheimer Disease'' (), RD Terry, R Katzman, KL Bick and SS Sisodia, Eds., Lippincott Williams and Wilkins, Philadelphia, PA, pp 233-243. * “Pathogenic protein strains as diagnostic and therapeutic targets in Alzheimer’s disease”. Walker LC, Rosen RF and LeVine III H (2012). In: ''Alzheimer's Disease: Targets for New Clinical Diagnostic and Therapeutic Strategies'' (), R Wegrzyn and AS Rudolph, Eds., CRC Press, Boca Raton, FL, pp 231-247. * “The prion-like properties of amyloid-β assemblies: Implications for Alzheimer’s disease”. Walker LC, Schelle J and Jucker M (2017). In: ''Prion Diseases'' (), SB Prusiner, Ed., Cold Spring Harbor Laboratory Press, pp 175-188. * “Prion-like protein seeding and the pathobiology of Alzheimer's disease”. Walker LC (2018). In: ''Protein Folding Disorders in the Central Nervous System'' (), J. Ghiso and A. Rostagno, Eds., World Scientific Publishing Company, pp 57-82.

References

External links

Seeded Aggregation and Transmissible Proteopathy—Creepy Stuff Not Just for Prions Anymore?
Retrieved 2020-04-16.
Abnormal proteins and Alzheimer's disease
Retrieved 2020-04-16.
Die Saat des Vergessens (Article on prion-like protein seeding in Alzheimer's disease)
Retrieved 2020-04-15.
Evidence of a ‘transmissible’ Alzheimer’s protein
Retrieved 2020-04-16.

Retrieved 2020-04-15. * ttps://www.dana.org/article/qa-with-lary-c-walker/ Q&A with Lary C. Walker, Ph.D.Retrieved 2020-05-04.
Protein Misfolding Diseases with Dr. Lary Walker
Retrieved 2020-05-04.
Alzheimer's, An Infectious Disease?
Retrieved 2020-05-04.
How do Neurodegenerative Diseases Progress?
Retrieved 2020-05-04.
Treatment from Brain Tissue May have Spread Alzheimer's Protein
Retrieved 2020-05-04.
Corrupted Proteins Spread Disease
Retrieved 2020-05-04.
Alzheimer's alphabet
Retrieved 2020-05-04. {{Authority control Living people Tulane University alumni Louisiana State University alumni Johns Hopkins University alumni Medical researchers Alzheimer's disease researchers Emory University faculty 1950 births