Alzheimer's research & therapy

TREM2 gene variants and related traits in Alzheimer's disease

Updated

Abstract

variant carriers (n = 123) show a faster cognitive decline compared to non-carriers (n = 1,459) despite similar clinical presentations at baseline.

  • Both groups had similar age and gender distributions, with carriers averaging 64 years and 54% female.
  • No significant differences were observed in cognitive assessments, neuropsychological domains, or various imaging and biomarker measures, except for less impaired visuospatial functioning in carriers.
  • TREM2 variant carriers experienced a cognitive decline rate of 0.6 points per year on the scale, approaching statistical significance.
  • R47H and T96K carriers exhibited notably faster cognitive decline compared to non-carriers, with R47H also associated with increased mortality post-diagnosis.
  • The findings suggest that while the clinical presentation is similar, the underlying genetic variants may influence the progression of Alzheimer's disease differently.

Simplified

Key numbers

−1.4
Cognitive Decline Increase
Points decline per year of follow-up for R47H carriers
1.60
Mortality Risk Increase
Hazard Ratio for mortality risk in R47H carriers
123 of 1582
Cohort Size
Variant carriers out of total AD patients in the cohort

Full Text

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Funding

Competing interests

Declarations. Ethics approval and consent to participate: The study was approved by the Medical Ethical Committee of Amsterdam UMC, location VUmc. All patients provided written informed consent for their clinical data to be used for research purposes. Consent was obtained according to the Declaration of Helsinki. Competing interests: S.L. is part of the GeneMINDS consortium, which is powered by Health~Holland, Top Sector Life Sciences & Health and receives co-financing from Vigil Neuroscience, Prevail therapeutics and Brain Research Center. All funding is paid to his institution. L.V. is supported by grant funding/collaborative study and consultancy/speaker fees from ZonMw (VENI grant), Amsterdam UMC (Startergrant) Stichting Dioraphte (biobank DemenTree), Olink, Lilly, and Roche; all paid to her institution. Research programs of W.F. have been funded by ZonMW, NWO, EU-JPND, EU-IHI, Alzheimer Nederland, Hersenstichting CardioVascular Onderzoek Nederland, Health~Holland, Topsector Life Sciences & Health, stichting Dioraphte, Gieskes-Strijbis fonds, stichting Equilibrio, Edwin Bouw fonds, Pasman stichting, stichting Alzheimer & Neuropsychiatrie Foundation, Philips, Biogen MA Inc, Novartis-NL, Life-MI, AVID, Roche BV, Fujifilm, Eisai, Combinostics. W.F. holds the Pasman chair. W.F. is recipient of TAP-dementia (www.tap-dementia.nl), receiving funding from ZonMw (#10510032120003). TAP-dementia receives co-financing from Avid Radiopharmaceuticals and Amprion. All funding is paid to her institution. W.F. has been an invited speaker at Biogen MA Inc, Danone, Eisai, WebMD Neurology (Medscape), NovoNordisk, Springer Healthcare, European Brain Council. All funding is paid to her institution. W.F. is consultant to Oxford Health Policy Forum CIC, Roche, Biogen MA Inc, and Eisai. All funding is paid to her institution. W.F. participated in advisory boards of Biogen MA Inc, Roche, and Eli Lilly. W.F. is member of the steering committee of EVOKE/EVOKE+ (NovoNordisk). All funding is paid to her institution. W.F. is member of the steering committee of PAVE, and Think Brain Health. W.F. was associate editor of Alzheimer, Research & Therapy in 2020/2021. W.F. is associate editor at Brain. R.O. has received research funding from European Research Council, ZonMw, NWO, National Institute of Health, Alzheimer Association, Alzheimer Nederland, Stichting Dioraphte, Cure Alzheimer’s fund, Health Holland, ERA PerMed, Alzheimerfonden, Hjarnfonden (all paid to the institutions). R.O. has received research support from Avid Radiopharmaceuticals, Janssen Research & Development, Roche, Quanterix and Optina Diagnostics, and has given lectures in symposia sponsored by GE Healthcare. He is an advisory board member for Asceneuron and Bristol Myers Squibb. All the aforementioned has been paid to the institutions. He is an editorial board member of Alzheimer’s Research & Therapy and the European Journal of Nuclear Medicine and Molecular Imaging. F.B. is Steering committee or Data Safety Monitoring Board member for Biogen, Merck, Eisai and Prothena. F.B. is advisory board member for Combinostics, Scottish Brain Sciences. F.B. is consultant for Roche, Celltrion, Rewind Therapeutics, Merck, Bracco. F.B. has research agreements with ADDI, Merck, Biogen, GE Healthcare, Roche. F.B. is co-founder and shareholder of Queen Square Analytics LTD.
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