The Pathology Core provides tissue diagnoses of Alzheimer's disease (AD), cerebrovascular disease (CVD) and related dementias and links the clinical studies with basic and translational research by project-driven, tissue procurement and allocation. During the current funding period, the Core served a total of funded 53 projects yielding 44 publications in peer review journals.
In AIM 1, the diagnostic protocol integrates the NIA-Reagan Institute Workshop Group protocol, components of the CERAD program, Braak and Braak parameters and the Aging Brain Program Project protocol, and global indicators of dementia.
AIM 2 : In the renewal, there are proposed projects of 19 investigators located at 9 academic centers. Relationship of aging, sex hormones, the retina and cerebral vasculature to dementia are areas of emphasis. Postmortem tissues are obtained from patients enrolled in the USC Clinical Core Brain Research Study and are all clinically defined by the UDS database. A twenty-four hour autopsy service minimizes postmortem delay insuring high-fidelity preparations for biochemistry and molecular biology, including mRNA expression profiling, and viable tissue for endothelial cell cultures. Following the ADC Biospecimen Best Practice Guidelines, tissue preparations are tailored to special protocols with reliable neuroanatomical dissections performed at autopsy. Postmortem tissues will be available for synaptoneurosome preparations to evaluate molecular pathology and plasticity changes of the synapse for four projects.
AIM 3 : Neuropathology summary reports are entered with the National Alzheimer's Coordinating Center (NACC).
AIM 4 : The Core will coordinate genotyping for risk factors, such as ApoE, from postmortem tissues and clinical blood samples.
AIM 5 : Training in the neuropathology of AD is extended to neuropathology fellows, neurology and pathology residents, and graduate students in neuroscience and pathobiology programs, both diagnostically and translational, emphasizing the neurobiology of dementia.
The Neuropathology Core confirms the presence of AD, vascular, and other types of neurodegenerative pathology will is essential to achieve most accurate etiological diagnosis. The Core is central for distributing human tissues for basic research into the cause and treatment of neurodegeneration disorders. The Core also provide a source of DNA for genomic wide association studies.
|Schneider, L S; Mangialasche, F; Andreasen, N et al. (2014) Clinical trials and late-stage drug development for Alzheimer's disease: an appraisal from 1984 to 2014. J Intern Med 275:251-83|
|Gatto, Nicole M; Henderson, Victor W; Hodis, Howard N et al. (2014) Components of air pollution and cognitive function in middle-aged and older adults in Los Angeles. Neurotoxicology 40:1-7|
|Finch, Caleb E; Beltrán-Sánchez, Hiram; Crimmins, Eileen M (2014) Uneven futures of human lifespans: reckonings from Gompertz mortality rates, climate change, and air pollution. Gerontology 60:183-8|
|Villeneuve, Sylvia; Reed, Bruce R; Wirth, Miranka et al. (2014) Cortical thickness mediates the effect of ?-amyloid on episodic memory. Neurology 82:761-7|
|Porsteinsson, Anton P; Drye, Lea T; Pollock, Bruce G et al. (2014) Effect of citalopram on agitation in Alzheimer disease: the CitAD randomized clinical trial. JAMA 311:682-91|
|Beecham, Gary W; Hamilton, Kara; Naj, Adam C et al. (2014) Genome-wide association meta-analysis of neuropathologic features of Alzheimer's disease and related dementias. PLoS Genet 10:e1004606|
|Schneider, Lon S (2014) Rethinking the Food and Drug Administration's 2013 guidance on developing drugs for early-stage Alzheimer's disease. Alzheimers Dement 10:247-50|
|Escott-Price, Valentina; Bellenguez, Céline; Wang, Li-San et al. (2014) Gene-wide analysis detects two new susceptibility genes for Alzheimer's disease. PLoS One 9:e94661|
|Cuajungco, Math P; Basilio, Luigi C; Silva, Joshua et al. (2014) Cellular zinc levels are modulated by TRPML1-TMEM163 interaction. Traffic 15:1247-65|
|Jayaraman, Anusha; Christensen, Amy; Moser, V Alexandra et al. (2014) Selective androgen receptor modulator RAD140 is neuroprotective in cultured neurons and kainate-lesioned male rats. Endocrinology 155:1398-406|
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