Wolfson Centre for Age-Related Diseases, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
University of Exeter Medical School, Exeter, UK.
Int J Geriatr Psychiatry. 2018 Aug;33(8):1146-1152. doi: 10.1002/gps.4908. Epub 2018 Jun 1.
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.
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.
We found both agitations and delusions to be significantly associated with increased tau pathology and decreased levels of ZnT3. ZnT3 packages Zn into synaptic vesicles to be released as a long-term modulator of synaptic activity.
Our finding adds to the evidence that zinc modulating compounds are of interest for treatment or symptomatic relief in these dementias.
在路易体痴呆和阿尔茨海默病中经常出现神经精神症状，如激越和妄想，这代表着巨大的负担和未满足的治疗需求。其潜在病因仍知之甚少。
我们使用多维线性模型，在路易体痴呆和阿尔茨海默病患者以及非痴呆对照者的死后组织中，对多个脑区的激越、妄想、淀粉样蛋白、tau 和 α-突触核蛋白以及突触蛋白（ZnT3、PSD95、突触小体蛋白和 β-III-微管蛋白）的测量值之间进行关联分析。
我们发现激越和妄想均与 tau 病理增加和 ZnT3 水平降低显著相关。ZnT3 将 Zn 包装到突触小泡中，作为突触活动的长期调节剂释放。
我们的发现增加了锌调节化合物在这些痴呆症的治疗或症状缓解方面具有重要意义的证据。
