The link between amyloid deposition in the brain and neurodegeneration and cognitive decline associated with Alzheimer’s disease (AD) is unclear, partly because similar amounts of brain amyloid have been detected in individuals with AD and age-matched individuals without cognitive impairment.

The researchers used 2D solid-state NMR spectroscopy to test whether the molecular structures of the amyloid beta (Aβ) fibrils, which are known to exist as polymorphs, are different between the two groups, thus accounting for the observed differences in neurodegeneration and cognitive deficit.

Autopsied brain tissues from individuals with high Aβ loads but no cognitive impairment revealed subtle but significant differences in the relative average populations of fibril polymorphs from previously published reports of fibril structures in cortical tissues from individuals with AD, even though similar fibril structures were detected in both groups.

The differences were more pronounced for fibrils of the Aβ42 isoform than for the Aβ40 isoform, raising the unverified possibility that the distribution of Aβ42 fibrils in cortical tissues may be a stronger predictor of cognitive impairment than that of Aβ40 fibrils.

According to the authors, although the study identifies subtle differences in Aβ fibrils in the two groups of individuals, factors besides Aβ polymorphism may determine cognitive status in AD.

https://www.pnas.org/content/118/45/e2111863118