Lary Walker

Lary Craswell Walker
Born	Columbus, Ohio, United States
Nationality	American
Alma mater	Louisiana State University (BS) Tulane University (MS, PhD)
Known for	Prion-like mechanisms in neurodegenerative diseases Neuropathology of Alzheimer's disease Proteopathy
Awards	Metlife 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	Neuroscience Neuropathology Neurology
Institutions	Tulane University Emory University Johns Hopkins University University of Greifswald Parke-Davis/Warner-Lambert University of Tübingen

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]}

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.
• "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.
• "Self-propagation of pathogenic protein aggregates in neurodegenerative diseases". Jucker M and Walker LC (2013). Nature 501: 45-51; PMID   24005412, PMCID: PMC3963807.
• "Neurodegenerative diseases: Expanding the prion concept". Walker LC and Jucker M (2015). Annual Review of Neuroscience 38: 87-103; PMID   25840008, PMCID: PMC4803040.
• "Proteopathic strains and the heterogeneity of neurodegenerative diseases". Walker LC (2016). Annual Review of Genetics 50: 329-346; PMID   27893962, PMCID: PMC6690197.
• "Propagation and spread of pathogenic protein assemblies in neurodegenerative diseases". Jucker M, Walker LC (2018). Nature Neuroscience 21: 1341-1349; PMID   30258241, 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; PMID   11238065, 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; PMID   16990547.

• "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.

• "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.

• "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.

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 ( 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". YouTube . 30 May 2014.
3. "Alexander von Humboldt Foundation".
4. "American Neuropsychiatric Association Annual Meeting 2017".
5. "Emory Goizueta ADRC Faculty and Staff".
6. 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. "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. PMC   11223644 . 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. S2CID   201656098.
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. PMC   9887729 . 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. Bibcode:2019PNAS..11626224H. 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. Bibcode:2013Natur.501...45J. 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. Bibcode:2014PNAS..111E4376H. 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. Bibcode:2019PNAS..11623029M. doi: 10.1073/pnas.1909322116 . PMC   6859373 . PMID   31641070.

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.
• Zwei Schritte vor, einen zurück (Article on the halting progress toward treatments for Alzheimer's disease) Retrieved 2020-04-15.
• 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.