@article{986fc01041734244aec5061b8c034a3f,
title = "Neurogranin in Alzheimer{\textquoteright}s disease and ageing: a human post-mortem study",
abstract = "Neurogranin (Ng), a post-synaptic protein involved in memory formation, has been investigated as a biomarker in the cerebrospinal fluid (CSF) in Alzheimer's disease (AD) and ageing. CSF Ng levels are elevated in AD relative to healthy controls and correlate with cognition; however, few studies have focused on Ng abundance in the brain. Synapse loss in the brain correlates closely with cognitive decline in AD making synaptic biomarkers potentially important for tracking disease progression, but the links between synaptic protein changes in CSF and brain remain incompletely understood. In the current study, Ng abundance was examined in post-mortem human brain tissue across AD, healthy ageing (HA), and mid-life (ML) cohorts. Ng levels were quantified in three brain regions associated with cognitive change found during ageing and neurodegenerative diseases, namely the middle temporal gyrus, primary visual cortex and the posterior hippocampus using immunohistochemistry. To support immunohistochemical analysis, total homogenate and biochemically enriched synaptic fractions from available temporal gyrus tissues were examined by immunoblot. Finally, we examined whether Ng is associated with lifetime cognitive ageing. Ng levels were significantly reduced in AD relative to HA and ML cases across all regions. Additionally Ng was significantly reduced in HA in comparison to ML in the primary visual cortex. Immunoblotting confirms reduced Ng levels in AD cases supporting immunohistochemical results. Interestingly, there was also a significant reduction of synapse-associated Ng in our group who had lifetime cognitive decline in comparison to the group with lifetime cognitive resilience indicating loss of neurogranin in remaining synapses during ageing is associated with cognitive decline. Our findings indicate that increases in CSF Ng reflect loss of brain neurogranin and support the use of CSF Ng as a biomarker of AD and potentially of cognitive decline in healthy ageing.",
keywords = "Ageing, Alzheimer's disease, Biomarker, Cerebrospinal fluid, Neurogranin, Post-synaptic",
author = "Tyler Saunders and Ciaran Gunn and Kaj Blennow and Hlin Kvartsberg and Henrik Zetterberg and Shenkin, {Susan Deborah} and Cox, {Simon R.} and Deary, {Ian J} and Colin Smith and Declan King and Tara Spires-Jones",
note = "Funding Information: KB is supported by the Swedish Research Council ( #2017-00915 ), the Alzheimer Drug Discovery Foundation (ADDF), USA ( #RDAPB-201809-2016615 ), the Swedish Alzheimer Foundation ( #AF-930351 , #AF-939721 and #AF-968270 ), Hj{\"a}rnfonden , Sweden ( #FO2017-0243 and #ALZ2022-0006 ), the Swedish state under the agreement between the Swedish government and the County Councils, the ALF-agreement (#ALFGBG-715986 and #ALFGBG-965240 ), the European Union Joint Program for Neurodegenerative Disorders ( JPND2019-466-236 ), the National Institute of Health (NIH), USA, (grant #1R01AG068398-01 ), and the Alzheimer's Association 2021 Zenith Award ( ZEN-21-848495 ). TSJ is supported by the UK Dementia Research Institute (UKDRI - Edin005) which receives its funding from DRI Ltd. , funded by the UK Medical Research Council , Alzheimer's Society, and Alzheimer's Research UK, the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (Grant agreement No. 681181 ), Alzheimer's Research UK ( ARUK-EG2016A-6 ), and a Wellcome Trust-University of Edinburgh Institutional Strategic Support Fund. Funding Information: HZ is a Wallenberg Scholar supported by grants from the Swedish Research Council ( #2018-02532 ), the European Research Council ( #681712 and #101053962 ), Swedish State Support for Clinical Research ( #ALFGBG-71320 ), the Alzheimer Drug Discovery Foundation (ADDF), USA ( #201809-2016862 ), the AD Strategic Fund and the Alzheimer's Association ( #ADSF-21-831376-C , #ADSF-21-831381-C and #ADSF-21-831377-C ), the Olav Thon Foundation , the Erling-Persson Family Foundation , Stiftelsen f{\"o}r Gamla Tj{\"a}narinnor, Hj{\"a}rnfonden, Sweden ( #FO2019-0228 ), the European Union's Horizon 2020 research and innovation programme under the Marie Sk{\l}odowska-Curie grant agreement No 860197 (MIRIADE), the European Union Joint Programme – Neurodegenerative Disease Research ( JPND2021-00694 ), and the UK Dementia Research Institute at UCL ( UKDRI-1003 ). Publisher Copyright: {\textcopyright} 2023 The Authors",
year = "2023",
month = feb,
doi = "10.1016/j.nbd.2023.105991",
language = "English",
volume = "177",
journal = "Neurobiology of disease",
issn = "0969-9961",
publisher = "Academic Press",
}