Alzheimer Disease

Matthew E. Peters, M.D., Constantine G. Lyketsos, M.D.


  • Alzheimer disease (AD) is a neurodegenerative disease and the most common cause of dementia.
    • AD is thought to account for at least 50% of dementia cases.[1]
    • Dementia is a syndrome characterized by global cognitive decline that significantly affects daily functioning in the absence of delirium.
  • There is growing recognition of individuals with cognitive impairment at a severity level insufficient for a diagnosis of dementia. Two terms have been used to describe these individuals:
    • Cognitive impairment, no dementia (CIND)
    • Mild cognitive impairment (MCI)
  • Cortical atrophy, amyloid-predominant neuritic plaques, tau-predominant neurofibrillary tangles, and neuronal death are hallmarks of the pathological diagnosis of AD confirmed via postmortem histopathological examination.[2]
  • Cascade view of etiopathogenesis of AD[3]:
    • Genetic and environmental risk factors interact to increase the production or to decrease the clearance of a toxic form of a peptide (amyloid beta (abeta) 1-42) derived from turnover of the amyloid precursor protein (APP), a transmembrane protein present on neurons.
    • If APP is processed through cleavage by β-secretase preferentially over α-secretase, this leads to the formation of abeta 1-42 that is prone to dimerization, oligomerization, and deposition in the extracellular space.
    • The deposited abeta 1-42 accumulates close to the synaptic cleft and is thought to lead over time to synaptic disconnection, the loss of neurotransmitter systems, and the emergence of symptoms.
  • Cognitive impairment due to AD is classified under the neurocognitive disorders (NCDs) section of the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5).[2]

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Last updated: March 1, 2017