In the healthy brain, the protein tau stabilizes neurotubules and is therefore essential for normal neural function. However, in Alzheimer disease (AD) and other neurodegenerative disorders, tau becomes abnormally hyperphosphorylated, dysfunctional, and misfolded, constituting the neurofibrillary tangles observed neuropathologically. In addition to tau tangles, β-amyloid neuritic plaques and neuronal loss are the other distinguishing neuropathologic characteristics of AD.
Positron emission tomography (PET) imaging tracers allowing for the measurement of β-amyloid in the brain have revolutionized the understanding of AD. Anatomically characteristic patterns of β-amyloid deposition can be recorded as many as 15 years before a person develops cognitive impairment.1 In a subset of the population, excess β-amyloid in the brain can be considered a major risk factor for AD, which could be modified with therapies aimed at removing β-amyloid during the critical period before subsequent neurodegenerative mechanisms render this approach useless.2,3 Defining when this critical period ends could be an important outcome of the completed clinical trials aimed at removing β-amyloid, which has been shown not to work once the patients have moderate impairment,4 and also of current trials targeting prodromal and even preclinical AD.2 However, the likelihood of success by removing β-amyloid could be even better defined by reaching a clearer understanding of the neurobiology of AD and, particularly, of the role of another neuropathologic constant of this disorder, the neurofibrillary tau tangles.
Masdeu JC. Tau and Cortical Thickness in Alzheimer Disease. JAMA Neurol. 2017;74(4):390–392. doi:10.1001/jamaneurol.2016.5701
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