Cerebral Blood Flow Dynamics in Neurodegenerative Diseases

The dynamic regulation of cerebral blood flow (CBF) is integral to neural function and energy homeostasis. In neurodegenerative diseases such as Alzheimer’s, Parkinson’s and frontotemporal dementia, alterations in microvascular perfusion and capillary regulation contribute to early cognitive decline and pathological progression. Dysfunction of pericytes and endothelial cells leads to capillary constriction, reduced perfusion and impaired clearance of toxic proteins. Simultaneously, compensatory vascular responses may temporarily preserve regional CBF, masking progressive hypoperfusion. These vascular changes interact with amyloid and tau pathology, exacerbating neuronal stress through oxidative damage and metabolic insufficiency. Understanding the complex interplay between vascular dysregulation and neurodegeneration has opened avenues for novel diagnostics, such as perfusion MRI biomarkers, and therapeutic strategies targeting vascular tone, endothelial integrity and blood–brain barrier function.

Research from Nature Portfolio

Recent studies have revealed the pivotal role of pericyte-mediated capillary tone in early Alzheimer’s disease. Using in vivo imaging in model mice, researchers demonstrated that L-type calcium channel inhibition relaxes pericytes, restores capillary diameter and improves cerebral perfusion, while reducing leukocyte stalling and tissue hypoxia. These findings suggest that modulating pericyte calcium influx may offer a therapeutic approach to sustain energy supply in affected brain regions. In a complementary data-driven analysis of large neuroimaging and biomarker datasets, investigators established that vascular dysregulation emerges prior to overt amyloid deposition and metabolic change in late-onset Alzheimer’s, indicating an early vascular stage in disease chronology. Moreover, experimental work in rats subjected to chronic bilateral carotid occlusion showed that sustained hypoperfusion accelerates amyloid-β accumulation, tau phosphorylation and reductions in glucose metabolism in hippocampal and cortical areas, thereby linking chronic vascular insufficiency to core pathological cascades.

Cerebral Blood Flow Dynamics in Neurodegenerative Diseases publication trend

The graph below shows the total number of articles in cerebral blood flow dynamics in neurodegenerative diseases across all publications each year (not limited to Nature Index journals).

Technical terms

Cerebral blood flow (CBF): The rate of arterial blood delivery to the brain, usually expressed in mL/100 g tissue/min, reflecting metabolic demand and vascular health.

Pericyte: A contractile cell that envelops capillaries and regulates capillary diameter, blood–brain barrier permeability and microvascular blood flow.

Hypoperfusion: A pathological reduction in blood flow to brain tissue, leading to energy deficit, hypoxia and potential neuronal injury.

Arterial spin labelling (ASL): A noninvasive MRI technique that uses magnetically labelled water protons in arterial blood as an endogenous tracer to measure CBF.

Neurovascular unit (NVU): The functional ensemble of neurons, astrocytes, pericytes, endothelial cells and extracellular matrix that coordinates cerebral blood flow and barrier function.

References

1. Inhibiting Ca2+ channels in Alzheimer’s disease model mice relaxes pericytes, improves cerebral blood flow and reduces immune cell stalling and hypoxia. Nature Neuroscience (2024).
2. The identification and cognitive correlation of perfusion patterns measured with arterial spin labeling MRI in Alzheimer’s disease. Alzheimer's Research & Therapy (2023).
3. Prospective Longitudinal Perfusion in Probable Alzheimer’s Disease Correlated with Atrophy in Temporal Lobe. Aging and Disease (2023).
4. Early role of vascular dysregulation on late-onset Alzheimer’s disease based on multifactorial data-driven analysis. Nature Communications (2016).
5. Capillary Dysfunction: Its Detection and Causative Role in Dementias and Stroke. Current Neurology and Neuroscience Reports (2015).
6. The effect of chronic cerebral hypoperfusion on the pathology of Alzheimer's disease: A positron emission tomography study in rats. Scientific Reports (2019).