Pathophysiological subtypes of mild cognitive impairment due to Alzheimer's disease identified by CSF proteomics.
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ABSTRACT:
SUBMITTER: Moutinho D
PROVIDER: S-EPMC11003166 | biostudies-literature | 2024 Apr
REPOSITORIES: biostudies-literature
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Pathophysiological subtypes of mild cognitive impairment due to Alzheimer's disease identified by CSF proteomics.
Moutinho Daniela D Mendes Vera M VM Caula Alessandro A Madeira Sara C SC Baldeiras Inês I Guerreiro Manuela M Cardoso Sandra S Gobom Johan J Zetterberg Henrik H Santana Isabel I De Mendonça Alexandre A Aidos Helena H Manadas Bruno B
Translational neurodegeneration 20240409 1
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Project description:Brain atrophy and altered CSF levels of amyloid beta (Abeta(42)) and the microtubule-associated protein tau are potent biomarkers of Alzheimer's disease (AD)-related pathology. However, the relationship between CSF biomarkers and brain morphometry is poorly understood. Thus, we addressed the following questions. (1) Can CSF biomarker levels explain the morphometric differences between normal controls (NC) and patients with mild cognitive impairment (MCI) or AD? (2) How are CSF biomarkers related to atrophy across the brain? (3) How closely are CSF biomarkers and morphometry related to clinical change [clinical dementia rating sum of boxes (CDR-sb)]? Three hundred seventy participants (105 NC, 175 MCI, 90 AD) from the Alzheimer's Disease Neuroimaging Initiative were studied, of whom 309 were followed for 1 year and 176 for 2 years. Analyses were performed across the entire cortical surface, as well as for 30 cortical and subcortical regions of interest. Results showed that CSF biomarker levels could not account for group differences in brain morphometry at baseline but that CSF biomarker levels showed moderate relationships to longitudinal atrophy rates in numerous brain areas, not restricted to medial temporal structures. Baseline morphometry was at least as predictive of atrophy as were CSF biomarkers. Even MCI patients with levels of Abeta(42) comparable with controls and of p-tau lower than controls showed more atrophy than the controls. Morphometry predicted change in CDR-sb better than did CSF biomarkers. These results indicate that morphometric changes in MCI and AD are not secondary to CSF biomarker changes and that the two types of biomarkers yield complementary information.
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Project description:BackgroundThe identification of the type and sequence of cognitive decline in preclinical mild cognitive impairment (MCI) prior to Alzheimer's disease (AD) is crucial for understanding AD pathogenesis and implementing therapeutic interventions.ObjectiveTo model the longitudinal courses of different neuropsychological functions in MCI due to AD.MethodsWe investigated the prodromal phase of MCI over a 12-year period in 27 initially healthy participants with subsequent MCI preceding AD (NC-MCI) and 60 demographically matched healthy individuals (NC-NC). The longitudinal courses of cognitive performance (verbal and visual episodic memory, semantic memory, executive functioning, constructional praxis, psychomotor speed, language, and informant-based reports) were analyzed with linear mixed effects models.ResultsThe sequence with which different cognitive functions declined in the NC-MCI relative to the NC-NC group began with verbal memory and savings performance approximately eight years, and verbal episodic learning, visual memory, and semantic memory (animal fluency) circa four years prior to the MCI diagnosis. Executive functioning, psychomotor speed, and informant-based reports of the NC-MCI group declined approximately two years preceding the MCI diagnosis.ConclusionsMeasurable neuropsychological deterioration occurs up to approximately eight years preceding MCI due to AD.
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