Deciphering the molecular and cellular underpinnings of cognitive resilience in Alzheimer’s disease
Our findings suggest that at the bulk tissue transcriptome level, cognitive resilience does not exhibit marked gene expression differences from healthy aging, despite significant Aβ and tau neuropathology. At the cellular level, specialized excitatory neuronal populations may drive cognitive resilience, while a specific subset of interneurons may play a crucial role in other forms of protection against AD-associated neuronal vulnerability. This systematic study provides direct insight into the molecular basis of cognitive resilience, yielding targets offering the potential to convert natural protective systems into effective therapeutic interventions for AD.
Authors
- Christoph Lange (ORCID: https://orcid.org/0000-0003-2620-1030)
- David Alan Bennett (ORCID: https://orcid.org/0000-0003-3689-554X)
- Dmitry Prokopenko (ORCID: https://orcid.org/0000-0002-1844-5652)
- Isabel Castanho (ORCID: https://orcid.org/0000-0003-1413-626X)
- Li‐Huei Tsai (ORCID: https://orcid.org/0000-0003-1262-0592)
- Rudolph E. Tanzi (ORCID: https://orcid.org/0000-0002-7032-1454)
- Lars Bertram
- Sarah Morgan (ORCID: https://orcid.org/0000-0002-1734-4710)
- Pourya Naderi Yeganeh (ORCID: https://orcid.org/0000-0002-4693-8331)
- Manolis Kellis (ORCID: https://orcid.org/0000-0001-7113-9630)
- Carles A. Boix (ORCID: https://orcid.org/0000-0001-9212-856X)
- Hansruedi Mathys (ORCID: https://orcid.org/0000-0003-0186-2115)
- Bartholomew White
Institutions
- Beth Israel Deaconess Medical Center (US)
- Harvard University (US)
- Queen Mary University of London (GB)
- University of Pittsburgh (US)
- University of Oslo (NO)
- Massachusetts General Hospital (US)
- Rush University (US)
- Massachusetts Institute of Technology (US)
- University of Lübeck (DE)
Publication Details
- Journal
- Alzheimer s & Dementia
- Published
- 2024-12-01
- DOI
- https://doi.org/10.1002/alz.090374
- Primary Topic
- Mitochondrial Function and Pathology
- Type
- article
- Field-Weighted Citation Impact
- 0.00