A Brief History of Tau

Featured Article : Goedert M, Spillantini MG, Jakes R, Rutherford D, Crowther RA. Multiple isoforms of human microtubule-associated protein tau: sequences and localization in neurofibrillary tangles of Alzheimer's disease. Neuron 1989;3:519–26.3Alzheimer disease (AD)4 is characterized by 2 kinds of abundant abnormal filamentous lesions, neuritic plaques and neurofibrillary tangles, seen in the brain post-mortem. The chief component of plaques is β-amyloid, a 40– to 42–amino acid proteolytic fragment of the amyloid precursor protein (APP). Rare mutations in the APP gene give rise to familial AD, but the vast majority of AD cases are sporadic, that is, without a dominant genetic cause. Cognitively normal people can show a large β-amyloid load, so simple accumulation of β-amyloid in the brain is not sufficient to lead to dementia, although APP mutations lead to a cascade of neuropathology, including tangles and eventually AD. There is a much clearer correlation between the number of neurofibrillary tangles found post-mortem and the degree of dementia observed in life, so it is important to understand the …