Mild Amyloid Pathology in the Primary Visual System of Nonagenarians and Centenarians

Abstract

In order to study the patterns of Alzheimer disease (AD)-related pathology in the primary visual system of the oldest old, we performed a quantitative analysis of senile plaques (SP), diffuse β amyloid (Aβ) deposit and neurofibrillary tangle (NFT) distribution in primary area 17, and a semi-quantitative analysis in the dorsal lateral geniculate nucleus (LGN), lateral inferior pulvinar (LIP) and superior colliculus (SC) of 21 individuals aged between 93 and 102 years. Among them, 10 cases were considered as non-demented (ND), while 9 presented very mild cognitive impairment (VMCI), and 2 cases had a clinical diagnosis of AD. Silver methenamine and Gallyas staining, Aβ and tau immunostaining revealed the distribution of AD lesions. In primary area 17, most cases, either ND or with VMCI displayed a low to medium number of SP. There was no significant difference in SP and Aβ deposit densities between ND and VMCI groups. On the whole, 0.4–2.4% of the cross-sectional cortical area was covered with Aβ deposits. Only 6 cases, either ND or with VMCI, were totally devoid of SP and diffuse Aβ deposits. Among the subcortical structures, the LIP and SC exhibited low densities of SP and Aβ deposits in about half of the ND and VMCI cases, while the LGN was totally spared. NFT were almost absent in area 17 and subcortical nuclei of ND and VMCI cases. These data imply that the ageing of the primary visual system in ND and VMCI nonagenarians and centenarians is characterised by the frequent development of mild amyloid pathology in area 17 in the absence of NFT. In agreement with previous studies in very old cohorts, they also suggest that amyloid deposition is not related to the early stages of the dementia process in the oldest old.

The neuropathological profile of mild cognitive impairment (MCI): a systematic review

“…33,53 In contrast, in other reports, MCI cases are found to be more similar and often indistinguishable from individuals with NCI. 20,22,36,44,[54][55][56][57][58][59][60][61][62][63] These results raise questions regarding the threshold necessary for the burden to be pathological and the existence of neural tolerance or compensation effects that may be related to the severity and location of the pathology (that is, hippocampus and EC spreading to the neocortex and primary visual system at later, more severe disease stages), the presence of disease comorbidity, brain reserve and donor age. 5,14,19,20,54,56,60,[64][65][66][67] Overall, despite variability in MCI definition, generally there is an increased presence of NFTs and NPs, although not always at the level associated with a neuropathological diagnosis of AD.…”

“…4,9,14,18,19,25,31,32,63,67,74,75 In some 19,20,44,76 reports, the volume of plaques seems to remain stable with disease progression, with significant changes only observed at late disease stages. These results have been taken to suggest that abnormal accumulation of plaques is not critical for the transition from NCI to MCI, 56 being necessary only for transitions to dementia. 20 However, the effect of amyloid deposition on cognitive function is understood to be mediated by plaque subtype (greater burden with neuritic vs diffuse plaques), 20,76,77 co-occurring NFT burden, 78 apolipoprotein E (APOE) e4 gene dosage, 18,41,42 age 42,56 and compensatory mechanisms linked to education level.…”

“…These results have been taken to suggest that abnormal accumulation of plaques is not critical for the transition from NCI to MCI, 56 being necessary only for transitions to dementia. 20 However, the effect of amyloid deposition on cognitive function is understood to be mediated by plaque subtype (greater burden with neuritic vs diffuse plaques), 20,76,77 co-occurring NFT burden, 78 apolipoprotein E (APOE) e4 gene dosage, 18,41,42 age 42,56 and compensatory mechanisms linked to education level. 79 Plaque-disease associations may also be missed because of methodological features.…”

Variation in NPC1, the gene encoding Niemann–Pick C1, a protein involved in intracellular cholesterol transport, is associated with Alzheimer disease and/or aging in the Polish population

“…Some amyloid deposits also develop in non-demented centenarians, e.g. in the visual cortex [20]. SLAD in the very old and centenarians shows distinctive distributions of plaques, tangles, and nerve death [10,13,14].…”

Perspectives on the Amyloid-β Cascade Hypothesis

“…In this regard, it is generally accepted that diffuse plaques (Aβ deposits without cores or a neuritic component) are decorative in nature, having little impact if any on cognitive function whereas neuritic plaques are more pathogenic. Parenthetically, often disregarded is the fact that Aβ deposits with a prominent fibrillar Aβ core (cored plaques) are numerous in the primary visual cortex of elderly individuals, again unassociated with dementia [60].…”