This study fractionated post-mortem hippocampus from 52 disease-free women aged 20 to 88 with SDS or sarkosyl and measured the insoluble proteins by mass spectrometry. Nearly all SDS-insoluble proteins declined with age, while about 300 sarkosyl-insoluble proteins increased, mostly after 80 (Fig. 1C–D). These proteins score high on phase-separation predictors and overlap with Alzheimer's plaque and tangle proteomes (Fig. 3).
Alternative hypothesis: The overlap with plaques and tangles reflects protein abundance rather than shared aggregation biology. Microdissected plaque and tangle proteomes recover mainly abundant proteins, and significant accumulators tend to be abundant, well-quantified proteins, so the enrichment in Fig. 3B may partly reflect detectability; abundance was controlled for the phase-separation result but not here. Separately, the steepest SDS decline falls between middle and old age (Fig. 1G), where donors switch mostly from one biobank to another, and the within-bank check was reported only for the sarkosyl accumulators.
Ideally, young and old donors would come from the same banks. Or, at minimum, two checks on existing data: plaque and tangle enrichment against an abundance-matched background, where persisting enrichment would support shared biology, and the SDS decline within each bank, where a persisting decline would point to aging rather than tissue source.