Increased Cerebrospinal Fluid Concentration of ZnT3 Is Associated with Cognitive Impairment in Alzheimer's Disease

BACKGROUND: Cognitive deficits arising in the course of Alzheimer's disease (AD), dementia with Lewy bodies (DLB), and Parkinson's disease with dementia (PDD) are directly linked to synaptic loss. Postmortem studies suggest that zinc transporter protein 3 (ZnT3), AMPA glutamate receptor 3 (GluA3), and Dynamin1 are associated with cognitive decline in AD and Lewy body dementia patients.

OBJECTIVE: We aimed to evaluate the diagnostic value of ZnT3, GluA3, and Dynamin 1 in the cerebrospinal fluid (CSF) of patients with dementia due to AD, DLB, and PDD compared to cognitively normal subjective cognitive decline (SCD) patients in a retrospective study. In addition, we assessed the relationship between synaptic markers and age, sex, cognitive impairment, and depressive symptoms as well as CSF amyloid, phosphorylated tau (p-tau), and total tau (T-tau).

METHODS: Commercially available ELISA immunoassay was used to measure the levels of proteins in a total of 97 CSF samples from AD (N = 24), PDD (N = 18), DLB (N = 27), and SCD (N = 28) patients. Cognitive impairment was assessed using the Mini-Mental State Examination (MMSE).

RESULTS: We found a significant increase in the concentrations of ZnT3, GluA3, and Dynamin1 in AD (p = 0.002) and of ZnT3 and Dynamin 1 in DLB (p = 0.001, p = 0.002) when compared to SCD patients. Changes in ZnT3 concentrations correlated with MMSE scores in AD (p = 0.011), and with depressive symptoms in SCD (p = 0.041).

CONCLUSION: We found alteration of CSF levels of synaptic proteins in AD, PDD, and DLB. Our results reveal distinct changes in CSF concentrations of ZnT3 that could reflect cognitive impairment in AD with implications for future prognostic and diagnostic marker development.

Medienart:

E-Artikel

Erscheinungsjahr:

2020

Erschienen:

2020

Enthalten in:

Zur Gesamtaufnahme - volume:77

Enthalten in:

Journal of Alzheimer's disease : JAD - 77(2020), 3 vom: 14., Seite 1143-1155

Sprache:

Englisch

Beteiligte Personen:

Enache, Daniela [VerfasserIn]
Pereira, Joana B [VerfasserIn]
Jelic, Vesna [VerfasserIn]
Winblad, Bengt [VerfasserIn]
Nilsson, Per [VerfasserIn]
Aarsland, Dag [VerfasserIn]
Bereczki, Erika [VerfasserIn]

Links:

Volltext

Themen:

Alzheimer’s disease
Biomarkers
Cation Transport Proteins
Cerebrospinal fluid
Cognitive impairment
Depression
Journal Article
Lewy body dementia
Research Support, Non-U.S. Gov't
SLC30A3 protein, human
Synaptic proteins
ZnT3

Anmerkungen:

Date Completed 09.09.2021

Date Revised 09.09.2021

published: Print

Citation Status MEDLINE

doi:

10.3233/JAD-200498

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM314971165