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,[5] and he is known for his research on the role of abnormal proteins in the causation of Alzheimer’s disease.[1][6]

Lary Craswell Walker
Born
Columbus, Ohio, United States
NationalityAmerican
Alma materLouisiana 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)[1][2]
Alexander von Humboldt Research Award (2016)[3]
Peter Bassoe Lectureship of the American Neuropsychiatric Association (2017)[4]
Scientific career
Fields
InstitutionsTulane University
Emory University
Johns Hopkins University
University of Greifswald
Parke-Davis/Warner-Lambert
University of Tübingen

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.[7][8] 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 is the Marie and E.R. Snelling Professor of Neurology.[9][10]

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.[11][12][13] 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).[14][15] Based on his work with animal models of Alzheimer's disease, Walker has proposed that humans are uniquely vulnerable to Alzheimer's disease.[16][17][18]

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, 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.[19][20][6] 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.[21] 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.[22][23][24]

Awards

Walker received the Metlife Foundation Award for Medical Research in Alzheimer's Disease in 2014,[1] the Alexander von Humboldt Research Award in 2016,[3] and the Peter Bassoe Lectureship of the American Neuropsychiatric Association in 2017.[4]

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

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. "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".
  3. "Alexander von Humboldt Foundation".
  4. "American Neuropsychiatric Association Annual Meeting 2017".
  5. "Emory Goizueta ADRC Faculty and Staff".
  6. "Could they all be prion diseases?".
  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: 35–51. doi:10.1111/j.1749-6632.1985.tb20798.x. PMID 2869729. S2CID 26512854.
  9. "Emory Neurology Faculty".
  10. "Emory Medicine Dean's Letter September 2016".
  11. 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. PMID 2828554. S2CID 25208183.
  12. Patrella, C; Grazia Di Certo, M; Barbato, C; Gabanella, F; Ralli, M; Greco, A; Possenti, R; Severini, C (2019). "Neuropeptides in Alzheimer's Disease: An Update". Current Alzheimer Research. 16 (6): 544–558. doi:10.2174/1567205016666190503152555. PMID 31456515.
  13. Hof, Patrick R. (1997). "Morphology and Neurochemical Characteristics of the Vulnerable Neurons in Brain Aging and Alzheimer's Disease". European Neurology. 37 (2): 71–81. doi:10.1159/000117414. ISSN 1750-1326. PMID 9058061.
  14. 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. PMID 8021711. S2CID 22652110.
  15. 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.
  16. 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.
  17. 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. doi:10.1073/pnas.1912954116. PMC 6936673. PMID 31871211.
  18. "Is Alzheimer's Disease a Uniquely Human Disorder?".
  19. Jucker, M; Walker, LC (2013). "Self-propagation of pathogenic protein aggregates in neurodegenerative diseases". Nature. 501 (7465): 45–51. doi:10.1038/nature12481. PMC 3963807. PMID 24005412.
  20. Knowles, TP; Vendruscolo, M; Dobson, CM (2014). "The amyloid state and its association with protein misfolding diseases". Nature Reviews Molecular Cell Biology. 15 (6): 384–396. doi:10.1038/nrm3810. PMID 24854788. S2CID 46357173.
  21. 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.
  22. 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.
  23. 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. doi:10.1073/pnas.1411649111. PMC 4205609. PMID 25261551.
  24. 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. doi:10.1073/pnas.1909322116. PMC 6859373. PMID 31641070.
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