Recent genetic studies of Alzheimer?s disease (AD) have focused our attention on the role of the innate immune system in disease susceptibility. However, the exact mechanism by which genetic variants dysregulate resident microglial cells and infiltrating monocytes that differentiate into macrophages to contribute to the development of AD remains unclear. Myeloid cells (microglia and macrophage) are highly plastic, responding to their environment to fulfill different functions that include the development and maintenance of synapses, control of inflammation and repair of the central nervous system (CNS) parenchyma. Emerging data highlight the heterogeneity of these cells that has, until now, been largely defined morphologically. In this application, we generate a new resource for the Alzheimer disease community: a collection of purified, cryopreserved aged human microglia from AD and non-AD brains that can be requested by ADRC and other investigators to support the investigation of a critical cell type for which access to live primary human cells has been an important limitation for the field.

Public Health Relevance

Alzheimer?s disease (AD) has recently been shown to be caused, in part, by a disturbance in the function of a type of brain cell called microglia which have many roles, including maintaining the function of other brain cells and protecting the brain from infection. In aging, these microglia begin to function less well; they have been hard to study in humans since they only live in the brain. In our proposal, we take pieces of brain from people who are recently deceased and isolate these important cells to create a biobank of well-characterized samples that other investigators can request to create new studies.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Specialized Center (P50)
Project #
5P50AG008702-30
Application #
9856965
Study Section
Special Emphasis Panel (ZAG1)
Program Officer
Silverberg, Nina B
Project Start
Project End
2021-05-31
Budget Start
2019-06-01
Budget End
2020-05-31
Support Year
30
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Columbia University (N.Y.)
Department
Type
DUNS #
621889815
City
New York
State
NY
Country
United States
Zip Code
10032
Wang, Tingyan; Qiu, Robin G; Yu, Ming (2018) Predictive Modeling of the Progression of Alzheimer's Disease with Recurrent Neural Networks. Sci Rep 8:9161
Agogo, George O; Ramsey, Christine M; Gnjidic, Danijela et al. (2018) Longitudinal associations between different dementia diagnoses and medication use jointly accounting for dropout. Int Psychogeriatr 30:1477-1487
Alosco, Michael L; Sugarman, Michael A; Besser, Lilah M et al. (2018) A Clinicopathological Investigation of White Matter Hyperintensities and Alzheimer's Disease Neuropathology. J Alzheimers Dis 63:1347-1360
Brent, Robert J (2018) Estimating the monetary benefits of medicare eligibility for reducing the symptoms of dementia. Appl Econ 50:6327-6340
Deming, Yuetiva; Dumitrescu, Logan; Barnes, Lisa L et al. (2018) Sex-specific genetic predictors of Alzheimer's disease biomarkers. Acta Neuropathol 136:857-872
Winawer, Melodie R; Griffin, Nicole G; Samanamud, Jorge et al. (2018) Somatic SLC35A2 variants in the brain are associated with intractable neocortical epilepsy. Ann Neurol 83:1133-1146
Tse, Kai-Hei; Cheng, Aifang; Ma, Fulin et al. (2018) DNA damage-associated oligodendrocyte degeneration precedes amyloid pathology and contributes to Alzheimer's disease and dementia. Alzheimers Dement 14:664-679
Schaffert, Jeff; LoBue, Christian; White, Charles L et al. (2018) Traumatic brain injury history is associated with an earlier age of dementia onset in autopsy-confirmed Alzheimer's disease. Neuropsychology 32:410-416
Qureshi, Yasir H; Patel, Vivek M; Berman, Diego E et al. (2018) An Alzheimer's Disease-Linked Loss-of-Function CLN5 Variant Impairs Cathepsin D Maturation, Consistent with a Retromer Trafficking Defect. Mol Cell Biol 38:
Reitz, Christiane (2018) Retromer Dysfunction and Neurodegenerative Disease. Curr Genomics 19:279-288

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