Alzheimer Dementia: Pathological indicators of Alzheimer's disease, the culprit of dementia

Although the deposition of fibrous starch β (Aβ) in the brain is considered to be one of the earliest pathological changes, it has occurred at least ten years before the clinical diagnosis of Alzheimer’s disease (AD) .

There are many explanations for the failure of AD treatment trials, especially in the course of the disease, the treatment is too late, the wrong target is targeted, or the treatment fails to contact the target correctly

Previous clinical pathological studies have strong evidence that age-related neuropathy accounts for 40% to 50% of changes in cognitive decline in later life, and pathological markers of AD account for 30% to 36% of changes

In addition, at the individual level, the proportion of AD pathology in the observed cognitive decline varies from 22% to 100%

With the development of in vivo assessment of AD pathological biomarkers, there is now convincing evidence that AD is a complex disease in its continuum ; Aβ, tau, and neurodegeneration are dynamic neuropathological factors.

Using multimodal neuroimaging, Duygu Tosun and others of the University of Pennsylvania explored the extent to which cognitive impairment and decline are Aβ and tau lesions and neurodegenerative levels detected by imaging markers.

They used partial least squares structural equation path model to evaluate imaging biomarkers (global Aβ-positron emission tomography [PET] uptake, regional tau-PET uptake and based Regional atrophy of magnetic resonance imaging) and risk factors (age, gender, education, lipoprotein E [APOE] and white matter impairment) have direct and indirect effects on cross-sectional cognitive impairment and longitudinal cognitive decline

They found that: in the cross section, Aβ accounted for 16% of the cognitive impairment variation, tau accounted for 46%-47%, atrophy accounted for 25%-29%, but 53%-58% of the total cognitive impairment variation was through the inclusion of AD risk The intermediary and direct influence of factors are explained

The Aβ-tau-atrophy pathway accounts for 50%-56% of the longitudinal cognitive decline variation, while Aβ, tau, and atrophy independently explain 16%, 46%-47%, and 25%-29% of the variation, respectively

These findings indicate that treatments that remove Aβ and completely stop the downstream effects on tau and neurodegeneration have only partial effects in slowing down cognitive decline or reversing cognitive impairment