Blood-Brain Barrier Breakdown in the Aging Human Hippocampus

By Axel Montagne, Samuel Barnes, Melanie D. Sweeney, Matthew R. Halliday, A. Sagare, Zhen Zhao, Arthur W. Toga, Russell E. Jacobs, Collin Y. Liu, Lilyana Amezcua and 4 more. Neuron, 2015

1,872 citations recorded by the source corpus.

Summary The blood-brain barrier (BBB) limits entry of blood-derived products, pathogens and cells into the brain that is essential for normal neuronal functioning and information processing. Post-mortem tissue analysis indicates BBB damage in Alzheimer’s disease (AD). The timing of BBB breakdown remains, however, elusive. Using an advanced dynamic contrast-enhanced magnetic resonance imaging protocol with high spatial and temporal resolutions to quantify regional BBB permeability in the living human brain, we show an age-dependent BBB breakdown in the hippocampus, a region critical for learning and memory that is affected early in AD. The BBB breakdown in the hippocampus and its CA1 and dentate gyrus subdivisions worsened with mild cognitive impairment that correlated with injury to BBB-associated pericytes, as shown by the cerebrospinal fluid analysis. Our data suggest that BBB breakdown is an early event in the aging human brain that begins in the hippocampus and may contribute to cognitive impairment.

Subfields: Cellular and Molecular Neuroscience, Neurology

View Paper: https://www.semanticscholar.org/paper/ecb503b57d66a952db93262d942c0d7fed311eb8

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In Cellular and Molecular Neuroscience

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Citations in the corpus

Brain metabolism in health, aging, and neurodegeneration (2017, neutral): “Cathepsin B induces the expression of BDNF in hippocampal neural progenitor cells, and the abilities of running to induce hippocampal neurogenesis and improve learning and memory performance are attenuated in cathepsin B-deficient mice (Moon et al, 2016) (Fig 5).”
A blood–brain barrier overview on structure, function, impairment, and biomarkers of integrity (2020, background): “These data are noteworthy from a clinical standpoint since the degeneration and injury of PCs have been reported in many neurological diseases, including Alzheimer’s disease (AD) [46–49], mild dementia [50], amyotrophic lateral sclerosis (ALS) [34], and stroke [35].”
Landmark-based deep multi-instance learning for brain disease diagnosis (2017, methodology): “Among various approaches, support vector machine (SVM), logistic regressors ( e.g. , Lasso, and Elastic Net ( Friedman et al., 2001 )), sparse representation based classiﬁcation (SRC) ( Wright et al., 2009 ), random forest classiﬁer ( Xiang et al., 2014; Moradi et al., 2015 ) are widely used.”
The blood–brain barrier in health and disease: Important unanswered questions (2020, background): “How do BBB properties change in age? Several studies have reported age-related decline in BBB function (Mooradian, 1988; Montagne et al., 2015; Erdő et al., 2017), and age-related pericyte dysfunction contributes to BBB permeability (Bell et al.”
β-Amyloid accumulation in the human brain after one night of sleep deprivation (2018, background): “Instead, changes in hippocampal volume, glucose metabolism (30), and the blood–brain barrier (46) were most evident in patients with early-stage AD.”