This Neuroathology Core (NP Core) has two components: One NPCore component is located at the University of California in San Francisco (UCSF) and the other is located at the University of Pennsylvania Medical Center (UPMC). Three main reasons for this arrangement are: (1) The overall theme of this ADRC is longitudinal comparisons of human frontotemporal lobar degenerative diseases (FTLD) and prion diseases with Alzheimer's disease, mild cognitive impairment, and normal control subjects enrolled in the ADRC. (2) UCSF has already had a long-standing FTDL collaboration with the UPML Laboratory. (3) Both Laboratories use unique morphological, immunohistochemical, and neurochemical methods to study these diseases, which makes this two component NP Core the ideal neuropathology adjunct to an ADRC that will emphasize studies of FTLDs and prion diseases. The UCSF NP Core assumes the main responsibility for obtaining autopsy brains, because the the subjects are recruited by the Clinical Core at UCSF and will likely die in the vicinity of UCSF. As such, the UCSF NP Core will perform the autopsies, obtain brain samples for research from the fresh brain, bank the research samples, prepare the remainder of the brain for standard neurohistopathological analysis, and send selected research and diagnostic brain samples from suspected FTLD cases to the UPMC NP Core component. Research samples, 2x2x1 cm, will be dissected bilaterally from the uncut brain at 15 cortical sites (Brodmann areas) known to either degenerate or be spared in FTLDs. In addition, similar samples will be obtained from the rotral (anterior) cigulate gyrus and the rostral insular cortex. These samples will be divided in half with one half immersion-fixed in paraformaldehyde for possible immunohistochemical studies and the other half frozen for neurochemical and molecular studies. These will be banked in the UCSF NPCore for use by investigators of the ADRC or other suitable outside investigators. The UCSF NP Core will use selected samples of this tissue to perform stereological estimates of synapse densities and nerve cell numbers. The rest of the brain and brainstem is formalin-fixed for neurohistopathological analysis to determine diagnosis using accepted diagnostic criteria.
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