title: The Roots of Alzheimer's Disease: Are High-Expanding Cortical Areas Preferentially Targeted?†.
abstract: Alzheimer's disease (AD) is regarded a human-specific condition, and it has been suggested that brain regions highly expanded in humans compared with other primates are selectively targeted. We calculated shared and unique variance in the distribution of AD atrophy accounted for by cortical expansion between macaque and human, affiliation to the default mode network (DMN), ontogenetic development and normal aging. Cortical expansion was moderately related to atrophy, but a critical discrepancy was seen in the medial temporo-parietal episodic memory network. Identification of "hotspots" and "coldspots" of expansion across several primate species did not yield compelling evidence for the hypothesis that highly expanded regions are specifically targeted. Controlling for distribution of atrophy in aging substantially attenuated the expansion-AD relationship. A path model showed that all variables explained unique variance in AD atrophy but were generally mediated through aging. This supports a systems-vulnerability model, where critical networks are subject to various negative impacts, aging in particular, rather than being selectively targeted in AD. An alternative approach is suggested, focused on the interplay of the phylogenetically old and preserved medial temporal lobe areas with more highly expanded association cortices governed by different principles of plasticity and stability.
authors.affiliation: Research Group for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo, 0373 Norway Department of Physical Medicine and Rehabilitation, Unit of Neuropsychology, Oslo University Hospital, 0424 Norway.
authors.forename: Anders M
authors.initials: AM
authors.lastname: Fjell
authors.affiliation: Research Group for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo, 0373 Norway.
authors.forename: Inge K
authors.initials: IK
authors.lastname: Amlien
authors.affiliation: Research Group for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo, 0373 Norway.
authors.forename: Markus H
authors.initials: MH
authors.lastname: Sneve
authors.affiliation: Research Group for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo, 0373 Norway.
authors.forename: Håkon
authors.initials: H
authors.lastname: Grydeland
authors.affiliation: Research Group for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo, 0373 Norway.
authors.forename: Christian K
authors.initials: CK
authors.lastname: Tamnes
authors.affiliation: Department of Physiology and Monash Vision Group, Monash University, Clayton, Victoria 3800, Australia ARC Centre of Excellence for Integrative Brain Function, Clayton, Victoria 3800, Australia.
authors.forename: Tristan A
authors.initials: TA
authors.lastname: Chaplin
authors.affiliation: Department of Physiology and Monash Vision Group, Monash University, Clayton, Victoria 3800, Australia ARC Centre of Excellence for Integrative Brain Function, Clayton, Victoria 3800, Australia.
authors.forename: Marcello G P
authors.initials: MG
authors.lastname: Rosa
authors.affiliation: Research Group for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo, 0373 Norway Department of Physical Medicine and Rehabilitation, Unit of Neuropsychology, Oslo University Hospital, 0424 Norway.
authors.forename: Kristine B
authors.initials: KB
authors.lastname: Walhovd
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000473:pathology*; D000544:Alzheimer Disease / Q000235:genetics / Q000473:pathology*; D000818:Animals; D001284:Atrophy / Q000473:pathology; D001931:Brain Mapping; D002540:Cerebral Cortex / Q000473:pathology*; D005260:Female; D006801:Humans; D008253:Macaca mulatta; D008297:Male; D008875:Middle Aged; D008959:Models, Neurological
keywords: Alzheimer's disease; aging; cerebral cortex; default mode network; evolution