Neuritic alterations and neural system dysfunction in Alzheimer's disease and dementia with Lewy bodies.
Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) are neurodegenerative disorders that share progressive dementia as the common major clinical symptom. Damages to memory-related brain structures are the likely pathological correlate, and in both illnesses deposition of amyloidogenic proteins are present mainly within these limbic structures. Amyloid-beta-positive plaques and phospho-tau-positive neurofibrillary tangles are the main feature of AD and alpha-synuclein-positive Lewy bodies and Lewy neurites are found in DLB. Interestingly the associated proteins also interfere with synaptic function and synaptic plasticity. Here, we propose that the same neuronal circuits are disturbed within the hippocampal formation in AD and DLB and that in both diseases the associated proteins might lead to changes in synaptic plasticity and function. Thus both classic neuropathological changes and cellular dysfunctions might contribute to the cognitive impairments in AD and DLB.
Alzheimer's Disease Research Laboratory, Harvard Medical School, Massachusetts General Hospital, Charlestown, Massachusetts, USA.
J
J
Klucken
P J
PJ
McLean
E
E
Gomez-Tortosa
M
M
Ingelsson
Bradley T
BT
Hyman
D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D006801:Humans; D020961:Lewy Body Disease / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D008569:Memory Disorders / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009410:Nerve Degeneration / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism; D009434:Neural Pathways / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D016501:Neurites / Q000473:pathology*; D009473:Neuronal Plasticity; D009435:Synaptic Transmission; D051843:Synucleins; D051844:alpha-Synuclein
D016229:Amyloid beta-Peptides; D009419:Nerve Tissue Proteins; C497604:SNCA protein, human; D051843:Synucleins; D051844:alpha-Synuclein