Open AccessAltered Tau and Neurofilament Proteins in Neuro‐Degenerative Diseases: Diagnostic Implications for Alzheimer's Disease and Lewy Body Dementias
Author(s) -
Trojanowski John Q.,
Schmidt Marie L.,
Shin RyongWoon,
Bramblett Gregory T.,
Rao Dinesh,
Lee Virginia M.Y.
Publication year - 1993
Publication title -
brain pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.986
H-Index - 132
eISSN - 1750-3639
pISSN - 1015-6305
DOI - 10.1111/j.1750-3639.1993.tb00725.x
Subject(s) - lewy body , neurofilament , neuroscience , disease , tau protein , alzheimer's disease , degenerative disease , cytoskeleton , biology , lewy body disease , pathology , dementia , medicine , dementia with lewy bodies , central nervous system disease , biochemistry , immunohistochemistry , cell
The neuronal cytoskeleton is one of the most profoundly altered organelles in late life neurodegenerative disorders that are characterized by progressive impairments in cognitive abilities. The elucidation of the protein building blocks of these organelles as well as advances in understanding how these proteins become altered in Alzheimer's disease (AD) and other less common dementing illnesses, i.e., diffuse Lewy body disease (DLBD) or the Lewy body variant of AD (LBVAD), will provide insights into the molecular basis of these disorders. Within, we review evidence that normal adult human tau is abnormally phosphorylated and converted into the subunits of AD paired helical filaments (PHFs), and that Lewy bodies (LBs) represent accumulation of altered neurofilament (NF) triplet subunits. Although the precise biological consequences of PHF and LB formation in neurons is unknown, growing evidence suggests that the formation of PHFs and LBs from normal neuronal cytoskeletal proteins could have deleterious effects on neuronal function and survival. Finally, insights into the composition of PHFs and LBs could lead to the development of novel strategies for the timely and accurate diagnosis of AD, DLBD and the LBVAD.