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Cell States and Neuronal Vulnerabilities in Neurodegenerative Diseases.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Cell States and Neuronal Vulnerabilities in Neurodegenerative Diseases./
作者:	Kamath, Tushar Vinod.
面頁冊數:	1 online resource (171 pages)
附註:	Source: Dissertations Abstracts International, Volume: 84-06, Section: B.
Contained By:	Dissertations Abstracts International84-06B.
標題:	Neurosciences. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=29394142click for full text (PQDT)
ISBN:	9798357576323

Cell States and Neuronal Vulnerabilities in Neurodegenerative Diseases.
Kamath, Tushar Vinod.

Cell States and Neuronal Vulnerabilities in Neurodegenerative Diseases. - 1 online resource (171 pages)

Source: Dissertations Abstracts International, Volume: 84-06, Section: B.

Thesis (Ph.D.)--Harvard University, 2022.

Includes bibliographical references

Neurodegenerative diseases are pathologically characterized by the induction of gliotic states and the loss of specific neurons in the human brain. A precise ascertainment of cellular states altered and those types of neurons that are lost has not been made in Alzheimer's and Parkinson's disease, the two most common forms of brain degeneration. We employed new single-cell genomic technologies to better understand the cellular alterations that occur in both these diseases. In Parkinson's disease, we developed a method to enrich midbrain dopaminergic neuronal nuclei from postmortem human samples. Using this strategy, we profiled thousands of these neurons to identify the diversity of these different types in the midbrain. Strikingly, we found one population, confined to the ventral tier of the pars compacta, was uniquely susceptible to Parkinson's-associated cell loss. This same population was enriched for common variant heritable risk of the disease, suggesting cell-autonomous mechanisms underlie the genetics of PD. To better understand the cellular alterations in Alzheimer's disease before death, we profiled individuals with suspected idiopathic normal pressure hydrocephalus (iNPH) with comorbid AD pathology. We identified two microglia populations, one increased and one decreased in abundance respectively, and confirmed these alterations in postmortem AD datasets. We further identified a single interneuron subpopulation residing in the uppermost layer of the neocortex as lost especially in the earliest stages of AD pathology. Finally, we find oligodendrocytes are an unrecognized contributor to beta-amyloid pathology. Measurement of beta-amyloid from stem cell-derived human oligodendrocytes confirmed that these cells are a significant producer of this important peptide. This body of work offers compelling evidence towards identifying the specific cellular state changes in association with two common brain diseases, offering new and testable hypotheses for future biological investigations into their pathogenesis.

Electronic reproduction.
Ann Arbor, Mich. :
ProQuest,
2023

Mode of access: World Wide Web

ISBN: 9798357576323Subjects--Topical Terms:

588700
Neurosciences.
Subjects--Index Terms:

Cell statesIndex Terms--Genre/Form:

542853
Electronic books.

Cell States and Neuronal Vulnerabilities in Neurodegenerative Diseases.
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