Fundamental questions remain in the search for the cause and treatment of Alzheimer disease (AD). As yet, it is not fully known what mechanisms trigger the sequence of neurologic changes that lead to neuronal death and dementia.1,2 An often-cited model proposes that APP in the brain is abnormally cleaved into smaller particles that produce a toxic β-amyloid peptide, which clump into extracellular plaques. The toxic effects of Aβ induce hyperphosphorylation of the microtubule-associated protein tau, causing neurofibrillary tangles, cell death, and subsequent dementia.3 Measures of these biomarkers can be obtained from cerebrospinal fluid and with neuroimaging. This model has been modified to allow a more complex temporal ordering of some biomarkers.4 More important, this model suggests that the disease begins decades before the onset of clinical symptoms. The most common risk factor is age. To date, no effective treatment has been found.5 Treatment that will delay or slow progression of AD likely will depend on early detection.
Howieson DB. Cognitive Decline in Presymptomatic Alzheimer Disease. JAMA Neurol. 2016;73(4):384–385. doi:10.1001/jamaneurol.2015.4993
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