The biological scaling of Alzheimer’s disease neuropathological changes across primate species

Toussaint C(1)(2), Bézard E(2), Lemoine M(#)(1), Planche V(#)(3)(4).

Author information:
(1)ImmunoConcEpT, CNRS UMR5164, Univ. Bordeaux, Bordeaux, F-33000, France.
(2)Institut des Maladies Neurodégénératives, CNRS UMR 5293, Univ. Bordeaux,
Bordeaux, F- 33000, France.
(3)Institut des Maladies Neurodégénératives, CNRS UMR 5293, Univ. Bordeaux,
Bordeaux, F- 33000, France. .
(4)Centre Mémoire Ressources Recherches, Service de Neurologie des Maladies
Neurodégénératives, Pôle de Neurosciences Cliniques, CHU de Bordeaux, Bordeaux,
F-33000, France. .
(#)Contributed equally

BACKGROUND: Studying the spontaneous emergence of biological anomalies within
the animal kingdom can provide insights into the causes of diseases. It is often
assumed that Alzheimer’s Disease (AD), like other neurodegenerative diseases, is
specific to humans. However, the age-related occurrence of AD neuropathological
changes (ADNC) in non-human primates (NHPs) and their comparison with humans has
not been formally studied. Moreover, a conceptual framework for interpreting the
spontaneous occurrence of ADNC in NHPs has yet to be established.
METHODS: We conducted a systematic review of the available data describing
spontaneous ADNC in various NHP species. To study the biological scaling of
ADNC, we used logistic regression models to compare NHP and human findings,
based on both chronological age and age standardized to each species’ maximum
longevity.
RESULTS: Amyloid plaques appear in all primate species according to the same
temporal dynamics once the theoretical maximum age is considered, and are
significantly more frequent in NHPs than in humans. In contrast, tau
neurofibrillary tangles are rare in NHPs and only appear at the limit of their
life expectancy.
CONCLUSION: The biological scaling of amyloid plaque development follows an
isometric model (proportional to lifespan), whereas tau tangles emerge at a
similar temporal horizon across primate species, regardless of lifespan (a
chronometric model). This temporal decoupling challenges the amyloid cascade
hypothesis as a universal, cross-species biological mechanism in late-onset
sporadic AD. The occurrence of full-blown ADNC may depend on the phylogenetic
temporal coupling of these two biological processes.

© 2025. The Author(s).

DOI: 10.1186/s13195-025-01889-2
PMID: 41219894

Conflict of interest statement: Declarations. Ethics approval and consent to
participate: Not applicable. Competing interests: E.B. is a director and
shareholder of Motac Neuroscience Ltd. During the past 3 years, V.P. was a local
unpaid investigator or sub-investigator for clinical trials granted by Novo
Nordisk, Biogen, Janssen, and Alector. V.P. served as a consultant for Motac
Neuroscience Ltd, outside the submitted work. Other authors declare no competing
interests.

Auteurs Bordeaux Neurocampus