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

Lookup NU author(s): Mary Johnson, Professor Johannes Attems, Dr Clive Ballard, Professor Alan ThomasORCiD, Professor John O'Brien, Dr Dag Aarsland

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Abstract

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 beta(A beta), tau, and alpha-synuclein at postmortem were used to investigate the relationship between ZnT3 and PSD95, cognition and pathology. Associations were observed between ZnT3 and PSD95 levels in prefrontal cortex and cognitive impairment (p = 0.001 and p = 0.002, respectively) and between ZnT3 levels in the parietal cortex and cognitive impairment (p = 0.036). Associations were also seen between ZnT3 levels in cingulate cortex and severity of Ab (p = 0.003) and tau (p = 0.011) pathologies. DLB and PDD were characterized by significant reductions of PSD95 (p < 0.05) and ZnT3 (p < 0.001) in prefrontal cortex compared with controls and AD. PSD95 levels in the parietal cortex were found to be decreased in AD cases compared with controls (p = 0.02) and PDD (p = 0.005). This study has identified Zn2+ modulation as a possible novel target for the treatment of cognitive impairment in DLB and PDD and the potential for synaptic proteins to be used as a biomarker for the differentiation of DLB and PDD from AD. (C) 2014 Elsevier Inc. All rights reserved.

Publication metadata

Author(s): Whitfield DR, Vallortigara J, Alghamdi A, Howlett D, Hortobagyi T, Johnson M, Attems J, Newhouse S, Ballard C, Thomas AJ, O'Brien JT, Aarsland D, Francis PT

Publication type: Article

Publication status: Published

Journal: Neurobiology of Aging

Year: 2014

Volume: 35

Issue: 12

Pages: 2836-2844

Print publication date: 01/12/2014

Online publication date: 17/06/2014

Acceptance date: 10/06/2014

ISSN (print): 0197-4580

ISSN (electronic): 1558-1497

Publisher: Elsevier

URL: http://dx.doi.org/10.1016/j.neurobiolaging.2014.06.015

DOI: 10.1016/j.neurobiolaging.2014.06.015

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