Cortical amyloid burden is associated with neuronal and vascular abnormalities. The retina shares significant structural and physiological similarities with the brain. This study assessed the association of retinal microstructural and microvascular signs with cortical amyloid burden in the prospective Atherosclerosis Risk in Communities-Positron Emission Tomography study. One hundred and twenty-four participants without a diagnosis of dementia underwent florbetapir PET (2011-13) and optical coherence tomography and optical coherence tomography angiography imaging (2017-19). Retinal nerve fibre thickness, total macular thickness and the ganglion cell-inner plexiform layer thickness were derived from the optical coherence tomography scan. Vessel density and the foveal avascular zone were measured on the 3 × 3 mm optical coherence tomography angiography scan. Amyloid burden, defined by global cortical standardized uptake value ratio, was treated as a dichotomous (standardized uptake value ratio > 1.2) and continuous outcome measure in logistic and robust linear regression models, respectively. Only lower intermediate capillary plexus vessel density [ (95% confidence interval) = -0.05 (-0.12, -0.01)] was significantly associated with increased continuous amyloid standardized uptake value ratio but not elevated dichotomous amyloid burden independently of demographic, genetic and vascular risk factors. No other retinal measure showed a significant association. Microvascular signs may accompany greater amyloid burden in late life in individuals without dementia.
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http://dx.doi.org/10.1093/braincomms/fcaf013 | DOI Listing |
Neurology
April 2025
L.C. Campbell Cognitive Neurology Research Unit, Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, ON, Canada.
Background And Objectives: Plasma biomarkers of Alzheimer disease (AD), neuroinflammation, and neurodegeneration are increasingly being used in clinical trials for diagnosis and monitoring of dementia. However, their association with longitudinal structural brain MRI changes, an important outcome measure across neurodegenerative and cerebrovascular diseases, is less known. We investigated how baseline plasma biomarkers reflect MRI markers of progression over time in patients with neurodegenerative and cerebrovascular diseases.
View Article and Find Full Text PDFNeurobiol Aging
March 2025
Department of Radiology, Mayo Clinic, Rochester, MN, USA. Electronic address:
Dementia with Lewy bodies (DLB) and posterior cortical atrophy (PCA) are neurodegenerative disorders that can overlap clinically and in patterns of regional hypometabolism and show elevated white matter hyperintensity (WMH) burden. Little is known about the regional WMH burden in DLB patients without any interference of AD pathology and how these patterns compare to PCA patients. Twenty-two amyloid-negative DLB patients, 40 amyloid-positive PCA patients, and 49 amyloid-negative cognitively unimpaired (CU) healthy individuals were recruited at Mayo Clinic, Rochester, MN.
View Article and Find Full Text PDFActa Neuropathol Commun
March 2025
Department of Neuroscience, University of Florida, Gainesville, FL-32610, USA.
Multiple lines of evidence indicate that immune signaling can impact the pathological progression in Alzheimer's disease (AD), including amyloid deposition, tau aggregation, synaptic pathology and neurodegenerative trajectory. In earlier studies, we reported that intracerebral expression of the anti-inflammatory cytokines, Interleukin-10 (Il10) and Interleukin-4 (Il4), increased amyloid β (Aβ) burden in TgCRND8 mice, a preclinical model of AD-type amyloidosis. As both Interleukin-10 receptor (IL10R) and Interleukin-4 receptor (IL4R) are upregulated in an age-progressive manner in rodent models of AD and in specific regions of human AD brains, we hypothesized that a decoy receptor strategy specifically targeting Il10 and Il4 signaling could have a disease-modifying effect.
View Article and Find Full Text PDFJ Clin Psychiatry
March 2025
Memory, Aging and Cognition Centre, Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
The underlying mechanisms of mild behavioral impairment (MBI), a marker for cognitive impairment and dementia, have remained unclear especially in a multiethnic Asian population. The study aimed to examine whether baseline Alzheimer disease biomarkers, including plasma neurofilament light (NfL) chain, phosphorylated tau-181 (p-tau181), and the p-tau181-to-amyloid-β42 (p-tau181/Aβ42) ratio, could predict MBI incidence in dementia-free Asian older adults. Participants were recruited from the community and memory clinics from August 2010 to April 2022.
View Article and Find Full Text PDFJAR Life
February 2025
Department of Neurosciences, University of California, San Diego, La Jolla, CA, USA.
Background: Older females have higher Alzheimer's Disease (AD) risk and tau burden, especially in early disease stages, compared to males. Overlapping cardiovascular disease (CVD) and dementia risk factors, like the apolipoprotein (APOE)-ε4 allele, show mixed sex-specific results. We previously found that late-life CVD risk related more strongly to tau at a single timepoint in cognitively normal, older female APOE-ε4 carriers than in males.
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