ArticleBrain pathology (Zurich, Switzerland)2016
Pathophysiology of Hypoperfusion of the Precuneus in Early Alzheimer's Disease.
Article in Brain pathology (Zurich, Switzerland), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers, 1 of them a synthesis that pooled it.
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Who cites it
71 citing papers in PubMed, 1 synthesis or guideline pooled it, 106 citations in OpenAlex.
- Functional MRI-Specific Alterations in Salience Network in Mild Cognitive Impairment: An ALE Meta-Analysis.Frontiers in aging neuroscience · 2021Pooled it
- Dysregulated TIE-2 expression is associated with blood-brain barrier leakiness and Alzheimer's disease-related neuropathology.Brain pathology (Zurich, Switzerland) · 2026Article
- Vessel-associated microglia are differentially activated and distributed in relation to systemic infection and Alzheimer's disease.Brain pathology (Zurich, Switzerland) · 2026Article
- Post-mortem evidence of pathogenic angiogenesis and abnormal vascular function in early Alzheimer's disease.Brain : a journal of neurology · 2026Article
- Enhancing diagnosis of mild cognitive impairment through brain-heart-gut metabolic networks in whole-body PET imaging.Cell reports. Medicine · 2026Article
- Cross-Sectional FDG in Down Syndrome and Autosomal Dominant Alzheimer's Disease.Annals of neurology · 2025Article
- CSF markers of vascular injury correlate with tau and cognitive decline in early Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Targeting the glymphatic system: Aβ accumulation and phototherapy strategies across different stages of Alzheimer's disease.Translational neurodegeneration · 2025Review
- Exploring the effect of pre-clinical Alzheimer's disease on blood pressure using Mendelian randomisation and parental dementia as an instrumental variable in UK Biobank.BMC medicine · 2025Article
- Alzheimer's Disease-Thrombosis Comorbidity: A Growing Body of Evidence from Patients and Animal Models.Cells · 2025Review
- Elevated vascular endothelial growth factor a is associated with disruption of default network connectivity in older adults.Brain imaging and behavior · 2025Article
- Single-Nucleus Landscape of Glial Cells and Neurons in Alzheimer's Disease.Molecular neurobiology · 2025Article
- Does white matter and vascular injury from repetitive head impacts lead to a novel pattern on T2 FLAIR MRI? A hypothesis proposal and call for research.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Review
- Cerebral perfusion correlates with amyloid deposition in patients with mild cognitive impairment due to Alzheimer's disease.The journal of prevention of Alzheimer's disease · 2025Article
- Combination treatment with cilostazol and isosorbide mononitrate attenuates microemboli-mediated vascular cognitive impairment and improves imaging and plasma biomarkers in diabetic rats.Experimental neurology · 2025Article
- Microangiopathy in temporal lobe epilepsy with diffusion MRI alterations and cognitive decline.Acta neuropathologica · 2024Article
- Three-dimensional pseudocontinuous arterial spin labeling with dual postlabeling delay for reflecting cerebral blood flow regulation in patients with hydrocephalus: a retrospective cross-sectional study.Quantitative imaging in medicine and surgery · 2024Article
- A single nuclear transcriptomic characterisation of mechanisms responsible for impaired angiogenesis and blood-brain barrier function in Alzheimer's disease.Nature communications · 2024Article
- Blockage of VEGF function by bevacizumab alleviates early-stage cerebrovascular dysfunction and improves cognitive function in a mouse model of Alzheimer's disease.Translational neurodegeneration · 2024Article
- Emerging Links between Cerebral Blood Flow Regulation and Cognitive Decline: A Role for Brain Microvascular Pericytes.Aging and disease · 2023Review
11 more citing papers are in PubMed but not listed here.
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3 authors at 1 institution in 1 country.
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Abstract
The earliest decline in cerebral perfusion in Alzheimer's disease (AD) is in the medial parietal cortex (precuneus). We have analyzed precuneus in post-mortem tissue from 70 AD and 37 control brains to explore the pathophysiology of the hypoperfusion: the contribution of arteriolosclerotic small vessel disease (SVD) and cerebral amyloid angiopathy (CAA), and of the vasoconstrictors endothelin-1 (EDN1) and angiotensin II (Ang II), and the association with Aβ. The myelin-associated glycoprotein:proteolipid protein-1 ratio (MAG:PLP1) was used as an indicator of oxygenation of the precuneus prior to death. MAG:PLP1 was reduced ∼50% in early AD (Braak stage III-IV). Although MAG:PLP1 remained low in advanced AD (stage V-VI), the reduction was less pronounced, possibly reflecting falling oxygen demand. Reduction in cortical MAG:PLP1 correlated with elevation in vascular endothelial growth factor (VEGF), another marker of hypoperfusion. Cortical MAG:PLP1 declined nonsignificantly with increasing SVD and CAA, but significantly with the concentration of EDN1, which was elevated approximately 75% in AD. In contrast, with reduction in cortical MAG:PLP1, Ang II level and angiotensin-converting enzyme (ACE) activity declined, showing a normal physiological response to hypoperfusion. MAG:PLP1 was reduced in the parietal white matter (WM) in AD but here the decline correlated positively (ie, physiologically) with WM EDN1. However, the decline of MAG:PLP1 in the WM was associated with increasing cortical EDN1 and perhaps reflected vasoconstriction of perforating arterioles, which traverse the cortex to perfuse the WM. EDN1 in the cortex correlated highly significantly with both soluble and insoluble Aβ42, shown previously to upregulate neuronal endothelin-converting enzyme-2 (ECE2), but not with Aβ40. Our findings demonstrate reduced oxygenation of the precuneus in early AD and suggest that elevated EDN1, resulting from Aβ42-mediated upregulation of ECE2, is a contributor.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.