Associations between ZnT3, tau pathology, agitation, and delusions in dementia

TY - JOUR

T1 - Associations between ZnT3, tau pathology, agitation, and delusions in dementia

AU - Whitfield, David R.

AU - Francis, Paul T.

AU - Ballard, Clive

AU - Williams, Gareth

PY - 2018/8/1

Y1 - 2018/8/1

N2 - Objective: Neuropsychiatric symptoms such as agitation and delusions occur frequently in Lewy body dementia and Alzheimer's disease and represent significant burden and unmet treatment need. The underlying aetiology remains poorly understood. Methods: We used a multidimensional linear model to look for associations between measurements of agitation, delusions, amyloid, tau and α-synuclein pathology, and synaptic proteins (ZnT3, PSD95, synaptophysin, and β-III-tubulin) across multiple brain regions in post-mortem tissue from a cohort of 130 Lewy body dementia and Alzheimer's disease patients and non-demented controls. Results: We found both agitations and delusions to be significantly associated with increased tau pathology and decreased levels of ZnT3. ZnT3 packages Zn2+ into synaptic vesicles to be released as a long-term modulator of synaptic activity. Conclusions: Our finding adds to the evidence that zinc modulating compounds are of interest for treatment or symptomatic relief in these dementias.

AB - Objective: Neuropsychiatric symptoms such as agitation and delusions occur frequently in Lewy body dementia and Alzheimer's disease and represent significant burden and unmet treatment need. The underlying aetiology remains poorly understood. Methods: We used a multidimensional linear model to look for associations between measurements of agitation, delusions, amyloid, tau and α-synuclein pathology, and synaptic proteins (ZnT3, PSD95, synaptophysin, and β-III-tubulin) across multiple brain regions in post-mortem tissue from a cohort of 130 Lewy body dementia and Alzheimer's disease patients and non-demented controls. Results: We found both agitations and delusions to be significantly associated with increased tau pathology and decreased levels of ZnT3. ZnT3 packages Zn2+ into synaptic vesicles to be released as a long-term modulator of synaptic activity. Conclusions: Our finding adds to the evidence that zinc modulating compounds are of interest for treatment or symptomatic relief in these dementias.

KW - Alzheimer's disease

KW - Lewy body dementia

KW - neuropsychiatric symptoms

KW - tau pathology

KW - zinc transporter 3

UR - http://www.scopus.com/inward/record.url?scp=85049803920&partnerID=8YFLogxK

U2 - 10.1002/gps.4908

DO - 10.1002/gps.4908

M3 - Article

AN - SCOPUS:85049803920

SN - 0885-6230

VL - 33

SP - 1146

EP - 1152

JO - International Journal of Geriatric Psychiatry

JF - International Journal of Geriatric Psychiatry

IS - 8

ER -