The intact postsynaptic protein neurogranin is reduced in brain tissue from patients with familial and sporadic Alzheimer's disease

Acta Neuropathologica
Hlin KvartsbergErik Portelius

Abstract

Synaptic degeneration and neuronal loss are early events in Alzheimer's disease (AD), occurring long before symptom onset, thus making synaptic biomarkers relevant for enabling early diagnosis. The postsynaptic protein neurogranin (Ng) is a cerebrospinal fluid (CSF) biomarker for AD, also in the prodromal phase. Here we tested the hypothesis that during AD neurodegeneration, processing of full-length Ng into endogenous peptides in the brain is increased. We characterized Ng in post-mortem brain tissue and investigated the levels of endogenous Ng peptides in relation to full-length protein in brain tissue of patients with sporadic (sAD) and familial Alzheimer's disease (fAD), healthy controls and individuals who were cognitively unaffected but amyloid-positive (CU-AP) in two different brain regions. Brain tissue from parietal cortex [sAD (n = 10) and age-matched controls (n = 10)] and temporal cortex [sAD (n = 9), fAD (n = 10), CU-AP (n = 13) and controls (n = 9)] were included and all the samples were analyzed by three different methods. Using high-resolution mass spectrometry, 39 endogenous Ng peptides were identified while full-length Ng was found to be modified including disulfide bridges or glutathione. In sAD parietal cort...Continue Reading

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Citations

May 18, 2019·Journal of Neurology, Neurosurgery, and Psychiatry·Kaj BlennowFranc Llorens
Nov 2, 2019·Alzheimer's & Dementia : the Journal of the Alzheimer's Association·Michelle M MielkeSilke Kern
Jul 16, 2020·Journal of Personalized Medicine·Chiara VillaRomina Combi
Mar 4, 2020·Alzheimer's Research & Therapy·Martí Colom-CadenaUNKNOWN Synaptic Health Endpoints Working Group
Nov 14, 2019·Neural Regeneration Research·Anna Villar-PiqueFranc Llorens
Apr 26, 2019·Molecular Neurobiology·Alberto Garrido-GarcíaF Javier Díez-Guerra
Nov 12, 2020·International Journal of Molecular Sciences·Maciej DulewiczBarbara Mroczko
Dec 7, 2020·Brain : a Journal of Neurology·Joana B PereiraOskar Hansson
Nov 30, 2020·Journal of Neurochemistry·Faisal Hayat NazirBruno Becker
Jan 1, 2021·Journal of Neurology, Neurosurgery, and Psychiatry·Steffen HalbgebauerMarkus Otto
Nov 21, 2020·International Journal of Molecular Sciences·Bin Zhou, Masanori Fukushima
Nov 19, 2020·Alzheimer's Research & Therapy·Victor BlonieckiYvonne Freund-Levi
Mar 5, 2021·Alzheimer's & Dementia : the Journal of the Alzheimer's Association·Michelle M MielkePrashanthi Vemuri
Mar 4, 2021·Alzheimer's Research & Therapy·Julia RemnestålAnna Månberg
Apr 6, 2021·Journal of Alzheimer's Disease : JAD·Nathalie Bodd HalaasKaj Blennow
May 1, 2021·International Journal of Molecular Sciences·Simona GribaudoSilvia De Marchis
May 15, 2021·Frontiers in Aging Neuroscience·Yulan FanUNKNOWN Alzheimer’s Disease Neuroimaging Initiative
Sep 27, 2020·Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases·Gabriel WestmanMarie Studahl
Sep 3, 2021·Journal of Neurochemistry·Eleni GkanatsiouGunnar Brinkmalm
Jan 12, 2022·Metabolic Brain Disease·Lalit SharmaDeepak Kumar

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Methods Mentioned

BETA
Protein Assay
immunoprecipitation
ELISA
acetylation

Software Mentioned

ImageJ
R
GraphPad Prism
SoftMax

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