Academic Journal
Differential amyloid-beta sensitivity across human and nonhuman primate neurons.
| Τίτλος: | Differential amyloid-beta sensitivity across human and nonhuman primate neurons. |
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| Συγγραφείς: | August I; University of California, San Diego, Department of Anthropology, 9500 Gilman Drive #0532, La Jolla, CA 92093, USA. Electronic address: iaugust@ucsd.edu., Steiner S; University of California, San Diego, Department of Neuroscience, 9500 Gilman Drive #0662, La Jolla, CA 92093, USA; Salk Institute for Biological Studies, 10010 North Torrey Pines Rd, La Jolla, CA 92037, USA., Oefner R; Salk Institute for Biological Studies, 10010 North Torrey Pines Rd, La Jolla, CA 92037, USA., Marchetto MC; University of California, San Diego, Department of Anthropology, 9500 Gilman Drive #0532, La Jolla, CA 92093, USA; Salk Institute for Biological Studies, 10010 North Torrey Pines Rd, La Jolla, CA 92037, USA. Electronic address: mcmarchetto@ucsd.edu. |
| Πηγή: | Journal of human evolution [J Hum Evol] 2026 Oct; Vol. 219, pp. 103888. Date of Electronic Publication: 2026 Aug 31. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Academic Press Country of Publication: England NLM ID: 0337330 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1095-8606 (Electronic) Linking ISSN: 00472484 NLM ISO Abbreviation: J Hum Evol Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: London ; New York : Academic Press |
| Ιατρικοί όροι (MeSH): | Amyloid beta-Peptides*/toxicity , Neurons*/drug effects , Alzheimer Disease*/physiopathology , Pan troglodytes* , Pan paniscus*, Animals ; Humans ; Macaca mulatta ; Induced Pluripotent Stem Cells ; Species Specificity |
| Περίληψη: | The human brain has undergone a threefold increase in size as well as changes in cytoarchitecture and neurochemical organization since the split with the last common ancestor with chimpanzees and bonobos. These changes have likely promoted increased cognitive flexibility but may also have come at the cost of increased vulnerability to neurodegenerative diseases like Alzheimer's disease (AD). Alzheimer's disease is the most common form of age-dependent dementia, and previous research suggests that humans may be uniquely vulnerable to AD. Primate comparative induced pluripotent stem cell models offer a unique opportunity to study the cellular and molecular mechanisms underlying this vulnerability. Plaques composed of amyloid-beta (aβ) are a hallmark pathology of AD, and while the exact role of aβ in disease pathogenesis remains incompletely understood, it is clear that aβ can have a neurotoxic effect and plays a role in the characteristic loss of neurons and synapses. Here we investigate susceptibility to aβ-induced toxicity in induced pluripotent stem cell-derived neurons from humans-both with and without AD, the two Pan species-a chimpanzee and a bonobo, and a rhesus macaque. To measure toxicity, we looked at cell death, along with other metrics of neuronal health and connectivity (neuritic beading and synaptic puncta density, respectively). We also employed transcriptomic approaches (RNA sequencing) to investigate molecular mechanisms underlying observed species differences. Our findings show that macaque neurons are less sensitive to aβ than human and ape neurons, and RNA sequencing points to molecular mechanisms that may underlie potentially protective responses in both macaque and ape neurons relative to humans. This work highlights the importance of studying AD from a comparative lens and provides insights into variation in susceptibility to AD among primates. (Copyright © 2026 The Authors. Published by Elsevier Ltd.. All rights reserved.) |
| Competing Interests: | Declaration of competing interest The authors declare that there is no conflict of interest that could be perceived as prejudicial to the impartiality of the reported research. |
| Contributed Indexing: | Keywords: Alzheimer’s disease; Evolution; NHPs; Plaques; iPSC |
| Substance Nomenclature: | 0 (Amyloid beta-Peptides) |
| Entry Date(s): | Date Created: 20260831 Date Completed: 20260930 Latest Revision: 20260930 |
| Update Code: | 20261001 |
| DOI: | 10.1016/j.jhevol.2026.103888 |
| PMID: | 42673741 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1095-8606 |
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| DOI: | 10.1016/j.jhevol.2026.103888 |