Toward a Unified Scheme for the Aggregation of Tau into Alzheimer Paired Helical Filaments

• Published in: Biochemistry (Easton) Vol. 41; no. 50; pp. 14885 - 14896
• Main Authors: Barghorn, S, Mandelkow, E
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 17.12.2002
• Subjects: Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Anions - chemistry; Arachidonic Acid - chemistry; Cross-Linking Reagents - chemistry; Cysteine - chemistry; Cysteine - genetics; Disulfides - chemistry; Heparin - chemistry; Humans; Mutagenesis, Site-Directed; Neurofibrillary Tangles - chemistry; Neurofibrillary Tangles - ultrastructure; Polymers - chemistry; Protein Isoforms - chemistry; Protein Isoforms - genetics; Protein Isoforms - metabolism; Protein Isoforms - ultrastructure; Protein Processing, Post-Translational - genetics; Spectrometry, Fluorescence; tau Proteins - chemistry; tau Proteins - genetics; tau Proteins - metabolism; tau Proteins - ultrastructure
• ISSN: 0006-2960; 1520-4995
• DOI: 10.1021/bi026469j

Alzheimer's disease is characterized by aggregates of tau protein. Attempts to study the conditions for aggregation in vitro have led to different experimental systems, some of which appear mutually exclusive (e.g., oxidative vs reductive conditions, induction by polyanions vs fatty acids). We show here that different approaches and pathways can be viewed in a common framework, and that apparent differences can be explained by variations in the kinetics of subreactions. A unified view of PHF aggregation should help to analyze the causes of PHF aggregation and devise methods to prevent it.