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 #
3P50AG008702-29S3
Application #
9633761
Study Section
Neuroscience of Aging Review Committee (NIA)
Project Start
Project End
Budget Start
2018-06-01
Budget End
2019-05-31
Support Year
29
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
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
Davis, Jeremy J (2018) Performance validity in older adults: Observed versus predicted false positive rates in relation to number of tests administered. J Clin Exp Neuropsychol 40:1013-1021
Tariciotti, Leonardo; Casadei, Matthew; Honig, Lawrence S et al. (2018) Clinical Experience with Cerebrospinal Fluid A?42, Total and Phosphorylated Tau in the Evaluation of 1,016 Individuals for Suspected Dementia. J Alzheimers Dis 65:1417-1425
Masucci, Michael D; Lister, Amanda; Corcoran, Cheryl M et al. (2018) Motor Dysfunction as a Risk Factor for Conversion to Psychosis Independent of Medication Use in a Psychosis-Risk Cohort. J Nerv Ment Dis 206:356-361
Crum, Jana; Wilson, Jeffrey; Sabbagh, Marwan (2018) Does taking statins affect the pathological burden in autopsy-confirmed Alzheimer's dementia? Alzheimers Res Ther 10:104
Lin, Ming; Gong, Pinghua; Yang, Tao et al. (2018) Big Data Analytical Approaches to the NACC Dataset: Aiding Preclinical Trial Enrichment. Alzheimer Dis Assoc Disord 32:18-27
Burke, Shanna L; Cadet, Tamara; Maddux, Marlaina (2018) Chronic Health Illnesses as Predictors of Mild Cognitive Impairment Among African American Older Adults. J Natl Med Assoc 110:314-325
Kirson, Noam Y; Scott Andrews, J; Desai, Urvi et al. (2018) Patient Characteristics and Outcomes Associated with Receiving an Earlier Versus Later Diagnosis of Probable Alzheimer's Disease. J Alzheimers Dis 61:295-307
Kamara, Dennis M; Gangishetti, Umesh; Gearing, Marla et al. (2018) Cerebral Amyloid Angiopathy: Similarity in African-Americans and Caucasians with Alzheimer's Disease. J Alzheimers Dis 62:1815-1826

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