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The Neuroscientist, Vol. 3, No. 2, 131-141 (1997)
DOI: 10.1177/107385849700300212

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The Neurofibrillary Pathology of Alzheimer's Disease

Michel Goedert

Medical Research Council Laboratory of Molecular Biology Cambridge

Abundant neurofibrillary lesions in certain brain regions constitute one of the defining neuropathological characteristics of Alzheimer's disease, where their presence correlates with the degree of dementia. An understanding of the mechanisms that lead to the neurofibrillary pathology is critical for elucidating the pathogenesis of Alzheimer's disease and for developing effective therapeutic strategies. Neurofibrillary lesions consist of neurofibrillary tangles, neuropil threads, and abnormal neurites. Ultrastructurally, each of these lesions consists of abnormal paired helical and straight filaments. These filaments are made of the six brain isoforms of microtubule-associated protein tau in a hyperphosphorylated and an abnormally phosphorylated state. Several candidate protein kinases and protein phosphatases for the hyperphos phorylation of tau have been identified. Moreover, recent results suggest that an interaction between tau protein and sulfated glycosaminoglycans may play an important role in inducing both the hyperphosphor ylation of tau and the formation of paired helical and straight filaments. NEUROSCIENTIST 3:131-141, 1997

Key Words: KEY WORDS Alzheimer's disease (AD) • Neurofibrillary lesions • Paired helical filament (PHF) • Tau protein • Phosphorylation • Sulfated glycosaminoglycans


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