Lary Walker is an American

neuroscientist A neuroscientist (or neurobiologist) is a scientist specializing in neuroscience that deals with the anatomy and function of neurons, Biological neural network, neural circuits, and glia, and their Behavior, behavioral, biological, and psycholo ...

and researcher at

Emory University Emory University is a private university, private research university in Atlanta, Georgia, United States. It was founded in 1836 as Emory College by the Methodist Episcopal Church and named in honor of Methodist bishop John Emory. Its main campu ...

Atlanta, Georgia Atlanta ( ) is the List of capitals in the United States, capital and List of municipalities in Georgia (U.S. state), most populous city in the U.S. state of Georgia (U.S. state), Georgia. It is the county seat, seat of Fulton County, Georg ...

. 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 and the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in remembering recent events. As the disease advances, symptoms can include problems wit ...

Education and career

Walker received his Bachelor of Science degree from

Louisiana State University Louisiana State University and Agricultural and Mechanical College, commonly referred to as Louisiana State University (LSU), is an American Public university, public Land-grant university, land-grant research university in Baton Rouge, Louis ...

, and his Master of Science and PhD degrees from

Tulane University The Tulane University of Louisiana (commonly referred to as Tulane University) is a private research university in New Orleans, Louisiana, United States. Founded as the Medical College of Louisiana in 1834 by a cohort of medical doctors, it b ...

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

University of Kassel The University of 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 professors. A special unit (Studienkoll ...

and a

National Institutes of Health The National Institutes of Health (NIH) is the primary agency of the United States government responsible for biomedical and public health research. It was founded in 1887 and is part of the United States Department of Health and Human Service ...

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

Johns Hopkins University The Johns Hopkins University (often abbreviated as Johns Hopkins, Hopkins, or JHU) is a private university, private research university in Baltimore, Maryland, United States. Founded in 1876 based on the European research institution model, J ...

, 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 Washtenaw County, Michigan, United States, and its county seat. The 2020 United States census, 2020 census recorded its population to be 123,851, making it the List of municipalities in Michigan, fifth-most populous cit ...

. 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 protein can enter the brain from the

cerebrospinal fluid Cerebrospinal fluid (CSF) is a clear, colorless Extracellular fluid#Transcellular fluid, transcellular body fluid found within the meninges, meningeal tissue that surrounds the vertebrate brain and spinal cord, and in the ventricular system, ven ...

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

animal models A model organism 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 workings of other organisms. Mod ...

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 (; ), is a public research university located in the city of Tübingen, Baden-Württemberg, Germany. The University of Tübingen is one of eleven German Excellenc ...

, 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 A prion () is a Proteinopathy, misfolded protein that induces misfolding in normal variants of the same protein, leading to cellular death. Prions are responsible for prion diseases, known as transmissible spongiform encephalopathy (TSEs), w ...

-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, is a class of diseases in which certain prote ...

' (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), also called frontotemporal degeneration disease or frontotemporal neurocognitive disorder, encompasses several types of dementia involving the progressive degeneration of the brain's frontal and temporal lobes. Men ...

, synucleinopathies such as

Parkinson's disease Parkinson's disease (PD), or simply Parkinson's, is a neurodegenerative disease primarily of the central nervous system, affecting both motor system, motor and non-motor systems. Symptoms typically develop gradually and non-motor issues become ...

and

Lewy Body Dementia Lewy body dementia (LBD) is an umbrella term for 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 ...

, systemic amyloidoses, and others.

Awards

Walker received the Metlife Foundation Award for Medical Research in Alzheimer's Disease in 2014, the Alexander von Humboldt Research Award in 2016, and the Peter Bassoe Lectureship of the American Neuropsychiatric Association in 2017.

Bibliography

Selected reviews

* "Seeds of Dementia". Walker LC and Jucker M (2013). ''Scientific American'' 308: 52-57; . * "Mechanisms of protein seeding in neurodegenerative diseases" Walker LC, Diamond MI, Duff KE and Hyman BT (2013). ''JAMA Neurology'' 70: 304-310; , PMCID: PMC3665718. * "Self-propagation of pathogenic protein aggregates in neurodegenerative diseases". Jucker M and Walker LC (2013). ''Nature'' 501: 45-51; , PMCID: PMC3963807. * "Neurodegenerative diseases: Expanding the prion concept". Walker LC and Jucker M (2015). ''Annual Review of Neuroscience'' 38: 87-103; , PMCID: PMC4803040. * "Proteopathic strains and the heterogeneity of neurodegenerative diseases". Walker LC (2016). ''Annual Review of Genetics'' 50: 329-346; , PMCID: PMC6690197. * "Propagation and spread of pathogenic protein assemblies in neurodegenerative diseases". Jucker M, Walker LC (2018). ''Nature Neuroscience'' 21: 1341-1349; , PMCID: PMC6375686.

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; , PMCID: PMC1850367. * "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; . * "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; , PMCID: PMC3045810. * "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; , PMCID: PMC3293176. * "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; , PMCID: PMC5724274.

Complete list of published work

* https://scholar.google.com/citations?user=Ap8lgXEAAAAJ&hl=en&oi=sra
nih.gov

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 American medical researchers Alzheimer's disease researchers Emory University faculty 1950 births