神经退行性疾病讲座.ppt

Neuropathology of Parkinson’s Disease with Dementia (CN) Neuropathology ofParkinson’s Disease Dementia James B. Leverenz, MD Associate ProfessorNeurology and Psychiatry and Behavioral SciencesUniversity of Washington School of Medicine UW Alzheimer’s Disease Research Center VA Northwest Network Mental Illness and Parkinson’s Disease Research, Education, and Clinical Centers Overview—Neuropathology of PDD Dementia in elderly PD patients is primarily due to Lewy body pathology, and not just coexistent AD Review of AD pathology Review of PD pathology Neuropathologic changes in PDD PDD is associated with severe deficits in the cholinergic system Biochemical and neuroimaging data Neuropsychologic data Abbreviations and Terminology PD – Parkinson’s Disease without dementia PDD – Parkinson’s Disease with dementia AD – Alzheimer’s Disease LBP – Lewy Body Pathology “classic” Lewy body inclusions alpha-synuclein immuno-positive inclusions and neurites CERAD – Consortium to Establish a Registry for Alzheimer’s Disease Alzheimer’s Disease—Pathology Pathological Criteria for AD Staging of AD pathologic change Neuritic plaques (CERAD, absent to frequent) Neurofibrillary tangles (Braak staging, I - VI) For pathological diagnosis of AD? Integrate CERAD and Braak staging evaluating “likelihood” AD changes led to dementia High - CERAD frequent/Braak V or VI Intermediate - CERAD moderate/Braak III or IV Low - CERAD sparse/Braak I or II AD Pathologic Change in Non-Demented Elderly Knopman et al (JNEN 2003)? 39 longitudinally followed non-demented cases Mean age 85 years (74 - 95) AD pathologic change 38 Braak stage I or greater, 4 Braak stage IV or V 37 with sparse or absent neuritic plaques, ~50% with moderate to frequent diffuse plaques “...cut off points ...Braak stage ≥ IV ...neuritic plaques ≥ moderate...” AD Pathologic Change in the Elderly Neuropathology of Parkinson’s Disease Substantia nigra pathology Improved Detection of Lewy Body Pathology Alpha-synuclein mu