Association of plasma A beta 40/A beta 42 ratio and brain A beta accumulation: testing a whole-brain PLS-VIP approach in individuals at risk of Alzheimer's disease

• Molecular and brain regional/network-wise pathophysiological changes at preclinical stages of Alzheimer's disease (AD) have primarily been found through knowledge-based studies conducted in late-stage mild cognitive impairment/dementia populations. However, such an approach may compromise the objective of identifying the earliest spatial-temporal pathophysiological processes. We investigated 261 individuals with subjective memory complaints, a condition at increased risk of AD, to test a whole-brain, non-a-priori method based on partial least squares in unraveling the association between plasma A beta 42/A beta 40 ratio and an extensive set of brain regions characterized through molecular imaging of A beta accumulation and cortical metabolism. Significant associations were mapped onto large-scale networks, identified through an atlas and by knowledge, to elaborate on the reliability of the results. Plasma A beta 42/beta 40 ratio was associated with A beta-PET uptake (but not FDG-PET) in regions generally investigated in preclinical AD such as those belonging to the default mode network, but also in regions/networks normally not accounted including the central executive and salience networks which likely have a selective vulnerability to incipient A beta accumulation. The present whole-brain approach is promising to investigate early pathophysiological changes of AD to fully capture the complexity of the disease, which is essential to develop timely screening, detection, diagnostic, and therapeutic interventions. (C) 2021 Elsevier Inc. All rights reserved.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Neurologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Neurology (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Psykiatri (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Psychiatry (hsv//eng)

Nyckelord

Subjective memory complaints

Preclinical Alzheimer's disease

Plasma

amyloid beta

Partial least square

whole-brain

variable selection methods

cognitive decline

clinical progression

amyloid deposition

network

connectivity

performance

biomarkers

validation

conversion

Geriatrics & Gerontology

Neurosciences & Neurology

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ref (ämneskategori)

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