Alzheimer's Disease Progression in the 5×FAD Mouse Captured with a Multiplex Gene Expression Array.

Background: Alzheimer's disease (AD) is an incurable complex neurodegenerative condition with no new therapies licensed in the past 20 years. AD progression is characterized by the up- and downregulation of distinct biological processes that can be followed through the expression level changes of associated genes and gene networks.

Objective: Our study aims to establish a multiplex gene expression tracking platform to follow disease progression in an animal model facilitating the study of treatment paradigms.

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

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.

Reduction of RPT6/S8 (a Proteasome Component) and Proteasome Activity in the Cortex is Associated with Cognitive Impairment in Lewy Body Dementia.

Lewy body dementia is the second most common neurodegenerative dementia and is pathologically characterized by α-synuclein positive cytoplasmic inclusions, with varying amounts of amyloid-β (Aβ) and hyperphosphorylated tau (tau) aggregates in addition to synaptic loss. A dysfunctional ubiquitin proteasome system (UPS), the major proteolytic pathway responsible for the clearance of short lived proteins, may be a mediating factor of disease progression and of the development of α-synuclein aggregates. In the present study, protein expression of a key component of the UPS, the RPT6 subunit of the 19S regulatory complex was determined.

Assessment of ZnT3 and PSD95 protein levels in Lewy body dementias and Alzheimer's disease: association with cognitive impairment.

The loss of zinc transporter 3 (ZnT3) has been implicated in age-related cognitive decline in mice, and the protein has been associated with plaques. We investigated the levels of ZnT3 and postsynaptic density protein 95 (PSD95), a marker of the postsynaptic terminal, in people with Parkinson's disease dementia (PDD, n = 31), dementia with Lewy bodies (DLB, n = 44), Alzheimer's disease (AD, n = 16), and controls (n = 24), using semiquantitative western blotting and immunohistochemistry in 3 cortical regions. Standardized cognitive assessments during life and semiquantitative scoring of amyloid β (Aβ), tau, and α-synuclein at postmortem were used to investigate the relationship between ZnT3 and PSD95, cognition and pathology.

Depression and synaptic zinc regulation in Alzheimer disease, dementia with lewy bodies, and Parkinson disease dementia.

Objective: Depression is a common symptom in dementia with Lewy bodies (DLB), Parkinson disease dementia (PDD), and Alzheimer disease (AD), yet its molecular basis remains unclear and current antidepressants do not appear to be effective. Cerebral zinc has been implicated in depression and synaptic dysfunction. We investigated the relationship between synaptic zinc regulation (for which zinc transporter 3 [ZnT3] is responsible) and depression in a large clinicopathologic study.