Detection of d-aspartate in tau proteins associated with Alzheimer paired helical filaments

• Published in: Brain research Vol. 675; no. 1; pp. 183 - 189
• Main Authors: Kenessey, Agnes, Yen, Shu-Hui, Liu, Wan-Kyng, Yang, Xiao-Ran, Dunlop, David S.
• Format: Journal Article
• Language: English
• Published: London Elsevier B.V 27-03-1995; Amsterdam Elsevier; New York, NY
• Subjects: Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Alzheimer's disease; Amino Acids - analysis; Amino Acids - metabolism; Aspartic Acid - analysis; Aspartic Acid - metabolism; Biological and medical sciences; Brain Chemistry - physiology; d-Aspartate; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Electrophoresis, Polyacrylamide Gel; Female; Humans; Hydrolysis; Immunoblotting; Medical sciences; Neurofibrillary Tangles - metabolism; Neurofibrillary Tangles - pathology; Neurology; Normal tau; PHF-tau; Pregnancy; tau Proteins - analysis; tau Proteins - metabolism; PHF-tau; Alzheimer's disease; Normal tau; d-Aspartate; Human; Nervous system diseases; D stereoisomer; Alzheimer disease; Paired helical filament; Central nervous system; Aspartate; Cerebral disorder; Tau protein; Central nervous system disease; Excitatory aminoacid; Neurotransmitter; Degenerative disease; Microtubule associated protein; Brain (vertebrata)
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/0006-8993(95)00061-T

Paired helical filaments (PHF) characteristic of Alzheimer neurofibrillary lesions are known to contain a modified form of microtubule associated protein tau. These proteins, PHF-tau, differ from normal tau in the extent and the site of phosphorylation. To determine whether PHF-tau, tau proteins from normal adult brains (N-tau), tau proteins from Alzheimer brains not associated with PHF (A-tau), and tau proteins from fetal brains (F-tau) differ in racemization, these proteins were compared for their
d-aspartate content. The results demonstrated that PHF-tau contain more
d-aspartate than N-tau, A-tau and F-tau. The average percentage
d-aspartate for these proteins, after a correction for background, are 4.9%, 2.8%, 1.6%, and 1% for PHF-tau, N-tau, A-tau and F-tau, respectively. It remains to be determined if the increase in
d-aspartate is a consequence of PHF formation. It is also unknown if the change in
d-aspartate content in PHF-tau is associated with phosphorylation, which alters the susceptibility of tau to proteolysis.