Lary Walker

Lary Craswell Walker
Born
Columbus, Ohio, United States
EducationLouisiana State University (BS)
Tulane University (MS, PhD)
Known forPrion-like mechanisms in neurodegenerative diseases
Neuropathology of Alzheimer's disease
Proteopathy
AwardsMetlife Foundation Award for Medical Research in Alzheimer's Disease (2014)
Alexander von Humboldt Research Award (2016)
Peter Bassoe Lectureship of the American Neuropsychiatric Association (2017)
Scientific career
Fields
WorkplacesTulane University
Emory University
Johns Hopkins University
University of Greifswald
Parke-Davis/Warner-Lambert
University of Tübingen

Lary Walker is an American neuroscientist and researcher in the field of neurodegenerative diseases. He is Professor Emeritus at Emory University in Atlanta, Georgia where he was Associate Director of the Goizueta Alzheimer's Disease Research Center. He is known for his research on the role of abnormal proteins in the causation of Alzheimer's disease.

Education and career

Walker received his Bachelor of Science degree from Louisiana State University and his Master of Science and PhD degrees from Tulane University. Following a German Academic Exchange (DAAD) Fellowship at the University of Kassel and a National Institutes of Health (NIH) postdoctoral fellowship at Emory University, he moved to the Neuropathology Laboratory of Donald L. Price at Johns Hopkins University, 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. In 2003 he returned to Emory University where he was the Marie and E.R. Snelling Professor of Neurology until transitioning to emeritus status in 2020.

Research

Biology of Aβ 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 Pharmaceuticals), he discovered that antibodies to the Aβ protein can enter the brain from the cerebrospinal fluid and selectively bind to Aβ plaques and cerebral Aβ-amyloid angiopathy (CAA). Based on his work with animal models 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 underlying the misfolding and aggregation of the Aβ protein in the brain. In collaboration with Mathias Jucker at the University of Tübingen, he discovered that the accumulation of Aβ can be initiated in transgenic mouse models by a prion-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' (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, synucleinopathies such as Parkinson's disease and Lewy Body Dementia, 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

Selected research reports

  • Meyer-Luehmann, M; Coomaraswamy, J; Bolmont, T; et al. (September 2006). "Exogenous induction of cerebral beta-amyloidogenesis is governed by agent and host". Science. 313: 1781–4. doi:10.1126/science.1131864. PMID 16990547..

Complete list of published work

Selected book chapters

  • "The neurobiology of aging in nonhuman primates". Walker LC and Cork LC (1999). In: Alzheimer Disease (ISBN 0781715032), 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 (ISBN 978-1-4398-2708-6), 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 (ISBN 978-1-621820-10-9), 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 (ISBN 978-981-3222-95-3), J. Ghiso and A. Rostagno, Eds., World Scientific Publishing Company, pp 57-82.

References

  1. 1 2 3 "MetLife Foundation Awards for Medical Research in Alzheimer's Disease" (PDF). Archived from the original (PDF) on 13 October 2018.
  2. ↑ "2014 MetLife Foundation Awards". YouTube. 30 May 2014.
  3. 1 2 "Alexander von Humboldt Foundation".
  4. 1 2 "ANPA Awards".
  5. ↑ "Emory Goizueta ADRC Faculty and Staff".
  6. 1 2 Miller, Greg (2009). "Could they all be prion diseases?". Science. 326 (5958): 1337–1339. Bibcode:2009Sci...326.1337M. doi:10.1126/science.326.5958.1337. PMID 19965731.
  7. ↑ "ORCID iD Lary Walker".
  8. ↑ Price, DL; Kitt, CA; Struble, RG; Whitehouse, PJ; Cork, LC; Walker, LC (1985). "Neurobiological studies of transmitter systems in aging and in Alzheimer-type dementia". Annals of the New York Academy of Sciences. 457 (1): 35–51. Bibcode:1985NYASA.457...35P. doi:10.1111/j.1749-6632.1985.tb20798.x. PMID 2869729. S2CID 26512854.
  9. ↑ Walker, LC; Kitt, CA; Cork, LC; Struble, RG; Dellovade, TL; Price, DL (1988). "Multiple transmitter systems contribute neurites to individual senile plaques". Journal of Neuropathology and Experimental Neurology. 47 (2): 138–144. doi:10.1097/00005072-198803000-00006. PMC 11223644. PMID 2828554. S2CID 25208183.
  10. ↑ Walker, LC (2020). "Abeta plaques". Free Neuropathology. 1:31 (epub 2020 Oct 30). doi:10.17879/freeneuropathology-2020-3025. PMID 33345256. S2CID 7745791.
  11. ↑ Walker, LC; Price, DL; Voytko, ML; Schenk, DB (1994). "Labeling of cerebral amyloid in vivo with a monoclonal antibody". Journal of Neuropathology and Experimental Neurology. 53 (4): 377–383. doi:10.1097/00005072-199407000-00009. PMC 9887729. PMID 8021711. S2CID 22652110.
  12. ↑ Masters, CL; Cappai, R; Barnham, KJ; Villemagne, VL (2006). "Molecular mechanisms for Alzheimer's disease: implications for neuroimaging and therapeutics". Journal of Neurochemistry. 97 (6): 1700–1725. doi:10.1111/j.1471-4159.2006.03989.x. PMID 16805778. S2CID 38283117.
  13. ↑ Walker, LC; Jucker, M (2017). "The exceptional vulnerability of humans to Alzheimer's disease". Trends in Molecular Medicine. 23 (6): 534–545. doi:10.1016/j.molmed.2017.04.001. PMC 5521004. PMID 28483344.
  14. ↑ Haque, RU; Levey, AI (2019). "Alzheimer's Disease: A Clinical Perspective and Future Nonhuman Primate Research Opportunities". Proceedings of the National Academy of Sciences USA. 116 (52): 26224–26229. Bibcode:2019PNAS..11626224H. doi:10.1073/pnas.1912954116. PMC 6936673. PMID 31871211.
  15. ↑ "Is Alzheimer's Disease a Uniquely Human Disorder?".
  16. ↑ Jucker, M; Walker, LC (2013). "Self-propagation of pathogenic protein aggregates in neurodegenerative diseases". Nature. 501 (7465): 45–51. Bibcode:2013Natur.501...45J. doi:10.1038/nature12481. PMC 3963807. PMID 24005412.
  17. ↑ Walker, LC; Jucker, M (2013). "Seeds of dementia". Scientific American. 308: 52–57. doi:10.1038/scientificamerican0513-52. PMC 10699165. PMID 23627220.
  18. ↑ Walker, LC; LeVine, H (2000). "The cerebral proteopathies". Neurobiology of Aging. 21 (4): 559–561. doi:10.1016/s0197-4580(00)00160-3. PMID 10924770. S2CID 54314137.
  19. ↑ Chen-Plotkin, Alice S.; Lee, Virginia M.-Y.; Trojanowski, John Q. (2010). "TAR DNA-binding protein 43 in neurodegenerative disease". Nature Reviews Neurology. 6 (4): 211–220. doi:10.1038/nrneurol.2010.18. ISSN 1759-4758. PMC 2892118. PMID 20234357.
  20. ↑ Holmes, BB; Furman, JL; Mahan, TE; Yamasaki, TR; Mirgaha, H; Eades, WC; Belaygorod, L; Cairns, NJ; Holtzman, DM; Diamond, MI (2014). "Proteopathic tau seeding predicts tauopathy in vivo". Proceedings of the National Academy of Sciences USA. 111 (41): E4376-85. Bibcode:2014PNAS..111E4376H. doi:10.1073/pnas.1411649111. PMC 4205609. PMID 25261551.
  21. ↑ Metrick, MA; do Carmo Ferreira, N; Saijo, E; Hughson, AG; Kraus, A; Orrú, C; Miller, MW; Zanusso, G; Ghetti, B; Vendruscolo, M; Caughey, B (2019). "Million-fold sensitivity enhancement in proteopathic seed amplification assays for biospecimens by Hofmeister ion comparisons". Proceedings of the National Academy of Sciences USA. 116 (46): 23029–23039. Bibcode:2019PNAS..11623029M. doi:10.1073/pnas.1909322116. PMC 6859373. PMID 31641070.