Neuropathological alterations in Alzheimer disease.
The neuropathological hallmarks of Alzheimer disease (AD) include "positive" lesions such as amyloid plaques and cerebral amyloid angiopathy, neurofibrillary tangles, and glial responses, and "negative" lesions such as neuronal and synaptic loss. Despite their inherently cross-sectional nature, postmortem studies have enabled the staging of the progression of both amyloid and tangle pathologies, and, consequently, the development of diagnostic criteria that are now used worldwide. In addition, clinicopathological correlation studies have been crucial to generate hypotheses about the pathophysiology of the disease, by establishing that there is a continuum between "normal" aging and AD dementia, and that the amyloid plaque build-up occurs primarily before the onset of cognitive deficits, while neurofibrillary tangles, neuron loss, and particularly synaptic loss, parallel the progression of cognitive decline. Importantly, these cross-sectional neuropathological data have been largely validated by longitudinal in vivo studies using modern imaging biomarkers such as amyloid PET and volumetric MRI.
Alzheimer Research Unit of the MassGeneral Institute for Neurodegenerative Disease, Department of Neurology of the Massachusetts General Hospital, and Harvard Medical School, Charlestown, Massachusetts, USA, 02129-4404.
Alberto
A
Serrano-Pozo
Matthew P
MP
Frosch
Eliezer
E
Masliah
Bradley T
BT
Hyman
D000375:Aging / Q000473:pathology; D000544:Alzheimer Disease / Q000175:diagnosis / Q000473:pathology* / Q000503:physiopathology; D016657:Cerebral Amyloid Angiopathy / Q000473:pathology / Q000503:physiopathology; D060825:Cognitive Dysfunction / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D020961:Lewy Body Disease / Q000473:pathology / Q000503:physiopathology; D008279:Magnetic Resonance Imaging; D016874:Neurofibrillary Tangles / Q000473:pathology / Q000502:physiology; D058225:Plaque, Amyloid / Q000473:pathology / Q000503:physiopathology; D049268:Positron-Emission Tomography