Andrea C. LeBlanc Pages 389 - 402 ( 14 )
Neuronal loss is associated with Alzheimers disease (AD). However, it not clear what type of mechanisms underlie this neuronal loss and if neuronal loss is directly responsible for the progressive dementia of AD. This review summarizes the recent evidence for neuronal loss in AD relative to the level of cognitive impairment. It further describes the current evidence for an apoptotic mechanism in AD. Lastly, a summary of the evidence for synaptic loss being responsible for dementia rather than neuronal loss is presented. A novel hypothesis emerges from this data to explain all aspects of AD pathophysiology. This all inclusive hypothesis called the attrition hypothesis states that activation of the effector caspase-6 in AD due to one or a variety of insults is responsible for the breakdown of the cytoskeletal structure of neurites and damages proper trafficking of proteins and organelles thus resulting in the observed clinical and pathological features of AD.
alzheimer disease, neuronal cell death, neurodegeneration, caspases, apoptosis, caspase
Bloomfield Center for Research in Aging, Lady Davis Institute for Medical Research, The Sir MortimerB Davis Jewish, General Hospital, 3755 Ch. Cote Ste-Catherine, Montreal, Quebec, Canada, H3T 1E2.