A cerebrospinal fluid synaptic protein biomarker for prediction of cognitive resilience versus decline in Alzheimer’s disease
Neurosciences Institute · Stanford University · +26 more institutions
Abstract
Rates of cognitive decline in Alzheimer’s disease (AD) are extremely heterogeneous. Although biomarkers for amyloid-beta (Aβ) and tau proteins, the hallmark AD pathologies, have improved pathology-based diagnosis, they explain only 20–40% of the variance in AD-related cognitive impairment (CI). To discover novel biomarkers of CI in AD, we performed cerebrospinal fluid (CSF) proteomics on 3,397 individuals from six major prospective AD case–control cohorts. Synapse proteins emerged as the strongest correlates of CI, independent of Aβ and tau. Using machine learning, we derived the CSF YWHAG:NPTX2 synapse protein ratio, which explained 27% of the variance in CI beyond CSF pTau181:Aβ42, 11% beyond tau positron…
Citation impact
- FWCI
- 75.01
- Percentile
- 100%
- References
- 91
Authors
38Topics & keywords
- Neurogranin
- Cerebrospinal fluid
- Cognitive decline
- Biomarker
- Hazard ratio
- Internal medicine
- Medicine
- Oncology
Funding
- NSNational Science FoundationAwards: RF1AG053303, U01AG058922, R01AG044546, RF1AG058501, P01AG003991
- AAAlzheimer's AssociationAwards: ZEN-22-848604, P50AG047366, ADSF-21-831377-C, 21-831377-C, P30AG10161, ZEN24-1069572, ADSF-21-831376-C, ADSF-24-1284328-C, ADSF-24-1284326-C, U24AG021886, SG-23-1061717, U24 AG021886, ADSF-21-831381-C
- CACure Alzheimer's Fund
- IYItä-Suomen Yliopisto
- EJEU Joint Programme – Neurodegenerative Disease ResearchAward: JPND2021-00694
- HCHope Center for Neurological Disorders
- AGAustralian Government
- EPEuropean Partnership on MetrologyAward: 22HLT07
- NINational Institute for Health and Care ResearchAwards: P30AG72975, R01AG15819, P30AG10161
- UCUniversity College LondonAward: UKDRI-1003
- ECEuropean CommissionAwards: 101096455, 328287, ALFGBG-71320, 860197, JPND2021-00694, 836089, 101053962
- LULunds Universitet
- KOKnut och Alice Wallenbergs StiftelseAward: 2022-0231
- VVetenskapsrådetAwards: 101053962, 2022-01018, 2022-00775, 2023-00356, FO2021-0293, 2019-02397, AF-980907, 1412/22, ALFGBG-71320
- SUSkånes universitetssjukhusAwards: 2022-1259, 2020-O000028, 2022-Projekt0080
- UDUK Dementia Research InstituteAward: UKDRI-1003
- OTOlav Thon Stiftelsen
- NINational Institutes of HealthAwards: 75N92022D00004, 75N92022D00005, 75N92022D00003, 75N92022D00001, U01AG46152, U01AG61356, P01AG03991, U01HL096812, U01HL096814, U01HL096899, U01HL096814, U01AG058922, P30AG72975, RF1AG053303, R01AG17917, U01HL096902, UL1TR003142, P30AG066515, U24AG021886, R01AG15819, P30AG066444, U01HL096899, R01AG044546, U24 AG021886, U01HL096812, P30AG10161, R21AG058859, P50AG047366, 75N92022D00002, U01HL096917, R01AG048076, P01AG003991, AG021886, P01AG026276, RF1AG058501
- PParkinsonfondenAward: 1412/22
- WTWu Tsai Neurosciences Institute, Stanford University
- HEHORIZON EUROPE Framework ProgrammeAwards: 101053962, 860197
- NINational Institute on AgingAwards: P01AG03991, U01HL096812, U01AG058922, P30AG066444, R21AG058859, U01HL096917, U01HL096814, AG072255, U01HL096902, R01AG17917, U01HL096899, RF1AG053303, P50AG047366, P01AG003991, U24AG021886, P30AG72975, RF1AG058501, R01AG048076, U01AG61356, R01AG044546, P30AG066515, R01AG15819, U01AG46152, U24 AG021886, P30AG10161, AG021886, P01AG026276
- NHNational Heart, Lung, and Blood InstituteAwards: U01HL096814, U01HL096902, 75N92022D00002, U01HL096917, 75N92022D00005, 75N92022D00003, 75N92022D00004, U01HL096899, U01HL096812, 75N92022D00001, 75N92022D00001, 75N92022D00002, 75N92022D00003
- NINational Institute on Deafness and Other Communication DisordersAwards: U01HL096812, U01HL096902, U01HL096917, U01HL096899, U01HL096814
- NINational Institute of Neurological Disorders and StrokeAward: R01AG044546