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<B>The Contribution of Age-Related Tauopathies to Alzheimer?s Disease.
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   Lead Investigator:    Michael Alosco
   Institution      :    Boston University
   E-Mail           :    malosco@bu.edu
   Proposal ID      :    1576
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   Proposal Description:
   <textarea name="description" rows="12" cols="85" wrap="virtual" readonly>Establishing an accurate neuropathological diagnosis is a critical function of Alzheimer?s Disease Center (ADC) Neuropathology Cores and is a prerequisite to all tissue-based research. Although chronic traumatic encephalopathy (CTE), primary age-related tauopathy (PART), argyrophilic grain disease (AGD) and aging-related tau astrogliopathy (ARTAG) are all age-related tauopathies, each has distinctive patterns of abnormal tau deposition. CTE, PART, and AGD are present in as many as 20 of brains found in neurodegenerative disease brain banks. ARTAG is a common co-morbidity in aged individuals. Criteria to diagnose CTE, PART, AGD and ARTAG have been recently proposed, yet no modules exist to capture these disorders in the National Alzheimer?s Disease Coordinating Center (NACC) database. Further, nuances in these pathological criteria may lead to diagnostic errors of omission and commission. Identification of unique tau and neuroinflammatory markers would help with the diagnosis and differentiation of CTE, PART, AGD, ARTAG from each other and from Alzheimer?s disease (AD) and may offer insights into disease mechanisms.  Furthermore, it is not known how much CTE, PART, AGD and ARTAG contribute to late life cognitive  decline. As much as 50 of cognitive decline can be explained by non-AD pathologies and these age-related tauopathies might account for the often heterogeneous presentations observed in neurodegenerative diseases. Without rigorous, reproducible protocols for the diagnosis of age-related tauopathies, disease-specific contributors to late life cognitive decline may be overlooked, confused and obscured.  Neuropsychiatric symptoms (NPS), including depression, anxiety, sleep disturbance, agitation and aggression are observed in age-related tauopathies (particularly CTE, AGD and PART). Several brain regions, including prefrontal cortex, uncal gyrus and amygdala, have been implicated in NPS, but are understudied in neurodegenerative diseases. We hypothesize that th </textarea>