Assessment of neurovascular uncoupling: APOE status is a key driver of early metabolic and vascular dysfunction.

Background: Alzheimer's disease (AD) is the most common cause of dementia worldwide, with apolipoprotein Eε4 (APOEε4) being the strongest genetic risk factor. Current clinical diagnostic imaging focuses on amyloid and tau; however, new methods are needed for earlier detection.

Methods: PET imaging was used to assess metabolism-perfusion in both sexes of aging C57BL/6J, and hAPOE mice, and were verified by transcriptomics, and immunopathology.

Assessment of Neurovascular Uncoupling: Status is a Key Driver of Early Metabolic and Vascular Dysfunction.

Background: Alzheimer's disease (AD) is the most common cause of dementia worldwide, with apolipoprotein ε4 () being the strongest genetic risk factor. Current clinical diagnostic imaging focuses on amyloid and tau; however, new methods are needed for earlier detection.

Methods: PET imaging was used to assess metabolism-perfusion in both sexes of aging C57BL/6J, and h mice, and were verified by transcriptomics, and immunopathology.

Cortical cerebrovascular and metabolic perturbations in the 5xFAD mouse model of Alzheimer's disease.

Introduction: The 5xFAD mouse is a popular model of familial Alzheimer's disease (AD) that is characterized by early beta-amyloid (Aβ) deposition and cognitive decrements. Despite numerous studies, the 5xFAD mouse has not been comprehensively phenotyped for vascular and metabolic perturbations over its lifespan.

Methods: Male and female 5xFAD and wild type (WT) littermates underwent F-fluorodeoxyglucose (FDG) positron emission tomography (PET) imaging at 4, 6, and 12 months of age to assess regional glucose metabolism.

The variant in methylenetetrahydrofolate reductase causes morphological and functional cerebrovascular deficits in mice.

Vascular contributions to cognitive impairment and dementia (VCID) particularly Alzheimer's disease and related dementias (ADRDs) are increasing; however, mechanisms driving cerebrovascular decline are poorly understood. Methylenetetrahydrofolate reductase (MTHFR) is a critical enzyme in the folate and methionine cycles. Variants in notably   are associated with dementias, but no mouse model existed to identify mechanisms by which increases risk.

Prophylactic evaluation of verubecestat on disease- and symptom-modifying effects in 5XFAD mice.

Introduction: Alzheimer's disease (AD) is the most common form of dementia. Beta-secretase (BACE) inhibitors have been proposed as potential therapeutic interventions; however, initiating treatment once disease has significantly progressed has failed to effectively stop or treat disease. Whether BACE inhibition may have efficacy when administered prophylactically in the early stages of AD has been under-investigated.

Interacts With High Fat/High Sugar Diet to Accelerate Alzheimer's Disease-Relevant Phenotypes in Mice.

Obesity is recognized as a significant risk factor for Alzheimer's disease (AD). Studies have supported the notion that obesity accelerates AD-related pathophysiology in mouse models of AD. The majority of studies, to date, have focused on the use of early-onset AD models.

Evaluation of chronic lead effects in the blood brain barrier system by DCE-CT.

Background: Lead (Pb) is an environmental factor has been suspected of contributing to the dementia including Alzheimer's disease (AD). Our previous studies have shown that Pb exposure at the subtoxic dose increased brain levels of beta-amyloid (Aβ) and amyloid plaques, a pathological hallmark for AD, in amyloid precursor protein (APP) transgenic mice, and is hypothesized to inhibit Aβ clearance in the blood- cerebrospinal fluid (CSF) barrier. However, it remains unclear how different levels of Pb affect Aβ clearance in the whole blood-brain barrier system.