Alzheimer's disease: a mini-review for the clinician

Abstract

Alzheimer's disease (AD), the most common form of dementia, is a striking example of the connection between neurophysiological abnormalities and higher-order cognitive deficiencies. Since its initial description in 1906, research into the pathophysiology and etiology of AD has led to the illumination of an incredibly complex set of genetic and molecular mechanisms for the disease's progression, characterized by much more than the neuropathological hallmarks of beta-amyloid (Aβ) plaques and neurofibrillary tangles (NFTs). In this review, findings relating the neurodegeneration present in AD to its clinical presentation and treatment are summarized, with an emphasis on the interconnectedness of disease pathophysiology. Further, diagnostic guidelines are provided based on the National Institute on Aging-Alzheimer's Association (NIA-AA) workgroup's clinical recommendations. Through the dissemination of detailed but digestible open access resources such as this one, we can move towards an increase in the equity and accessibility of education for the modern clinician.

Keywords: Alzheimer’s disease; diagnosis; history; medicine; neurodegeneration; pathophysiology.

Figure 1

Graphical representation of the three primary pathophysiological manifestations of Alzheimer’s disease. (A) The amyloid plaque in the cerebral cortex is formed as a result of APP cleavage to form the Amyloid-beta monomer, which can subsequently form soluble oligomers. These oligomers can exert neurotoxic effects as they are, but may also assemble into insoluble protofibrils and later fibrils, which compose the plaques. (B) Depicted within a pyramidal neuron of the hippocampus, the neurofibrillary tangle (NFT) is localized to the cell body and results from the hyperphosphorylation of tau protein, which aggregates into paired helical filaments (PHFs). (C) Death of basal forebrain cholinergic neurons is a prominent marker of Alzheimer’s disease.

Figure 2

Workflow for Alzheimer’s disease diagnosis following All-Cause Dementia diagnosis, using the clinical guidelines of the National Institute on Aging and the Alzheimer’s Association.