title: Tau phosphorylation in human brain: relationship to behavioral disturbance in dementia.
abstract: Agitation and aggressive behavior are common symptoms of Alzheimer's disease (AD), and tangle density in frontal cortex is a possible regional substrate of these behaviors. To investigate this further, 16 AD patients, 8 patients with non-AD dementia, and 13 age-matched control subjects for frontal cortex and, respectively, 21, 7, and 6 patients for parietal cortex were analyzed for tau and phospho-tau by enzyme-linked immunosorbent assay (ELISA). Agitation/aggression was determined by the Present Behavioural Examination. In a subset of cases, glycogen synthase kinase-3β (GSK-3β) phosphorylation and protein phosphatase 2A (PP2A) expression were measured. Phospho-tau and the phospho-tau/total tau ratio were elevated in AD in both cortical regions. In keeping with our hypothesis, the phospho-tau/total tau ratio was elevated in the frontal cortex of those patients with agitation/aggression during life, and there was a significant correlation (p = 0.024) between these behaviors and the phospho-tau/total tau ratio in the cortex. PP2A expression was lower (p < 0.01) in the frontal cortex of patients with high tau phosphorylation. This study confirms a link between tau phosphorylation and agitation/aggression and suggests that reducing tau phosphorylation may provide symptomatic relief.
authors.affiliation: King's College London, Wolfson Centre for Age-Related Diseases, London, UK.
authors.forename: Simone
authors.initials: S
authors.lastname: Guadagna
authors.forename: Margaret M
authors.initials: MM
authors.lastname: Esiri
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Williams
authors.forename: Paul T
authors.initials: PT
authors.lastname: Francis
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology*; D000704:Analysis of Variance; D001921:Brain / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D003704:Dementia / Q000378:metabolism / Q000473:pathology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation / Q000502:physiology; D013223:Statistics as Topic; D018709:Statistics, Nonparametric; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016875:tau Proteins; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3