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.
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Overactivity and/or aggressiveness in Alzheimer's disease are associated with decreased cholinergic markers, particularly in frontal and temporal cortex, and with decreased serotonin and serotonin metabolites.
“All three studies concur: overactivity and/or aggressiveness were associated with decreased cholinergic markers, particularly in frontal and temporal cortex, and with decreased serotonin and serotonin metabolites.”
From Neuropsychiatric symptoms in Alzheimer's disease: what might be associated brain circuits? (2015) · cites this paper as Guadagna et al., 2012
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- Authors
- Guadagna, S., Esiri, M. M., Williams, R. J., & Francis, P. T.
- Affiliations
- King's College London (GB)
- University of Oxford (GB)
- Corresponding author
- Francis, Paul T.
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 2012-12
- Volume
- 33
- Issue
- 12
- Pages
- 2798-2806
- ISSN
- 0197-4580 (ISSN-L)
- OpenAlex
- W1996208240
- Cited by
- 48
- References
- 44
- Citations by year
- 2026: 5 · 2025: 3 · 2024: 4 · 2022: 1 · 2021: 3 · 2020: 2 · 2019: 4 · 2018: 4 · 2017: 6 · 2016: 2 · 2015: 5 · 2014: 4 · 2013: 4 · 2012: 1
- FWCI
- 3.00
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurobiology of Aging (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- H. Lundbeck A/S
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- tau phosphorylation, Alzheimer's disease, dementia, agitation, aggression, behavioral problems, frontal cortex, parietal cortex, glycogen synthase kinase-3β, protein phosphatase 2A, neurofibrillary tangles
- MeSH terms
- Glycogen Synthase Kinase 3 beta, Aged, Aged, 80 and over, Alzheimer Disease, Analysis of Variance, Brain, Dementia, Enzyme-Linked Immunosorbent Assay, Female, Humans, Male, Middle Aged, Phosphorylation, Statistics as Topic, tau Proteins, Statistics, Nonparametric, Glycogen Synthase Kinase 3
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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