The association of Alzheimer's disease and cerebrovascular disease biomarkers towards the neurodegeneration of the cholinergic pathways. (31st December 2021)

• Record Type: Journal Article
• Authors: Cedres, Nira; Ferreira, Daniel; Nemy, Milan; Machado, Alejandra; Pereira, Joana B.; Wahlund, Lars‐Olof; Zettergren, Anna; Teipel, Stefan J.; Grothe, Michel J.; Eriksdotter, Maria; Stepankova, Olga; Vyslouzilova, Lenka; Blennow, Kaj; Zetterberg, Henrik; Kern, Silke; Skoog, Ingmar; Westman, Eric
• Is Part Of: Alzheimer's & dementia. Volume 17(2021)Supplement 5
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-12-31
• Subjects: Alzheimer's disease -- Periodicals; Alzheimer Disease -- Periodicals; Dementia -- Periodicals; Démence; Maladie d'Alzheimer; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.83
• DOI: 10.1002/alz.054885
• Languages: English
• ISSNs: 1552-5260

Abstract

Abstract: Background: To determine the contribution of amyloid pathology and tau pathology in combination with cerebrovascular pathology, towards the neurodegeneration of the cholinergic white matter projections. Method: We included a sample of 203 cognitively unimpaired individuals derived from the H70 Gothenburg Birth Cohort Studies (all of them 70‐years‐old, 51% female). Amyloid (A) and tau (T) pathology were determined by cerebrospinal fluid levels of Amyloid‐β42/40 ratio, Amyloid‐β38 and phosphorylated tau. Cerebrovascular pathology (V) was determined by automatically segmented white matter lesions detected in magnetic resonance imaging (MRI). Cholinergic white matter projections (i.e. cingulum pathway and external capsule pathway) were modelled using tractography based on diffusion tensor imaging data. Sex and APOE ε4 carriership were also included in the analysis. To assess association of the markers with the integrity of cholinergic projections we used random forest regression Result: white matter lesion burden was the most important contributor towards the neurodegeneration of both cholinergic pathways (figure 1). Levels of Amyloid‐β38 and phosphorylated tau also contributed to the cholinergic pathways, especially to the external capsule pathway. Amyloid‐β42/40 ratio levels and APOE ε4 carriership did not show substantial contribution. Females showed poorer integrity in the external capsule pathway. Conclusion: Underlying cerebrovascular disease (V) in cognitively unimpaired elderly plays a central role in the neurodegeneration (N) of the cholinergic pathways to the cerebral cortex. Future research should elucidate the impact of cerebrovascular pathology to the cholinergic disruption and cognitive impairment in pathological populations.