Journal
ALZHEIMERS & DEMENTIA
Volume 17, Issue 6, Pages 946-958Publisher
WILEY
DOI: 10.1002/alz.12345
Keywords
amyloid beta peptide; human neocortex; label‐ free liquid chromatography tandem mass spectrometry; pathologically diagnosed preclinical Alzheimer' s disease; proteomics; symptomatic Alzheimer' s disease
Categories
Funding
- Fonds Wetenschappelijk Onderzoek Vlaanderen [FWO G0F8516N, G065721N]
- Vlaamse Impulsfinanciering voor Netwerken voor Dementie-onderzoek [IWT 135043]
- RUN (KU Leuven) [RUN/16/001]
- C1 (FOscil
- KU Leuven)
- DIP-BiD (Hercules/FWO) [AKUL/15/40 - G0H2116N]
- EU [01ED1203F, 01ED1512]
- German Federal Ministry of Education and Research [FTLDc 01GI1007A]
- German Federal Ministry of Education and Research (German Research Foundation/DFG) [SFB1279]
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Proteome profile changes in Alzheimer's disease brains involve early-responding, late-responding, gradually-changing, and fraction-shifting proteins. Gene ontology analysis indicates vesicle endocytosis and the secretory pathway as early-involved components in AD.
Proteome profile changes in Alzheimer's disease (AD) brains have been reported. However, it is unclear whether they represent a continuous process, or whether there is a sequential involvement of distinct proteins. To address this question, we used mass spectrometry. We analyzed soluble, dispersible, sodium dodecyl sulfate, and formic acid fractions of neocortex homogenates (mainly Brodmann area 17-19) from 18 pathologically diagnosed preclinical AD, 17 symptomatic AD, and 18 cases without signs of neurodegeneration. By doing so, we identified four groups of AD-related proteins being changed in levels in preclinical and symptomatic AD cases: early-responding, late-responding, gradually-changing, and fraction-shifting proteins. Gene ontology analysis of these proteins and all known AD-risk/causative genes identified vesicle endocytosis and the secretory pathway-related processes as an early-involved AD component. In conclusion, our findings suggest that subtle changes involving the secretory pathway and endocytosis precede severe proteome changes in symptomatic AD as part of the preclinical phase of AD. The respective early-responding proteins may also contribute to synaptic vesicle cycle alterations in symptomatic AD.
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