Dataset Information

Hypertension drives parenchymal ?-amyloid accumulation in the brain parenchyma.

ABSTRACT: There is substantial controversy regarding the causative role of amyloid ? (A?) deposition in Alzheimer's disease (AD). The cerebrovasculature plays an important role in the elimination of A? from the brain and hypertension is a well-known risk factor for AD. In spontaneously hypertensive stroke-prone rats (SHRSP), an animal model of chronic arterial hypertension, cerebral small vessel disease (CSVD) leads to age-dependent parenchymal A? accumulation similar to that observed in AD. These data approve the neuropathological link between CSVD and AD, confirm the challenge that parenchymal A? deposition is a specific marker for AD and disclose the meaning of SHRSP as valid experimental model to investigate the association between hypertension, CSVD, and A? plaques.

SUBMITTER: Bueche CZ

PROVIDER: S-EPMC4212487 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature

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Hypertension drives parenchymal β-amyloid accumulation in the brain parenchyma.

Bueche Celine Z CZ Hawkes Cheryl C Garz Cornelia C Vielhaber Stefan S Attems Johannes J Knight Robert T RT Reymann Klaus K Heinze Hans-Jochen HJ Carare Roxana O RO Schreiber Stefanie S

Annals of clinical and translational neurology 20140109 2

There is substantial controversy regarding the causative role of amyloid β (Aβ) deposition in Alzheimer's disease (AD). The cerebrovasculature plays an important role in the elimination of Aβ from the brain and hypertension is a well-known risk factor for AD. In spontaneously hypertensive stroke-prone rats (SHRSP), an animal model of chronic arterial hypertension, cerebral small vessel disease (CSVD) leads to age-dependent parenchymal Aβ accumulation similar to that observed in AD. These data ap ...[more]

PMID: 25356391

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Project description:Microglia are brain-resident myeloid cells and play a major role in the innate immune responses of the CNS and the pathogenesis of Alzheimer's disease (AD). However, the contribution of nonparenchymal or brain-infiltrated myeloid cells to disease progression remains to be demonstrated. Here, we show that monocyte-derived cells (MDC) invade brain parenchyma in advanced stages of AD continuum using transcriptional analysis and immunohistochemical characterization in post-mortem human hippocampus. Our findings demonstrated that a high proportion (60%) of demented Braak V-VI individuals was associated with up-regulation of genes rarely expressed by microglial cells and abundant in monocytes, among which stands the membrane-bound scavenger receptor for haptoglobin/hemoglobin complexes or Cd163. These Cd163-positive MDC invaded the hippocampal parenchyma, acquired a microglial-like morphology, and were located in close proximity to blood vessels. Moreover, and most interesting, these invading monocytes infiltrated the nearby amyloid plaques contributing to plaque-associated myeloid cell heterogeneity. However, in aged-matched control individuals with hippocampal amyloid pathology, no signs of MDC brain infiltration or plaque invasion were found. The previously reported microglial degeneration/dysfunction in AD hippocampus could be a key pathological factor inducing MDC recruitment. Our data suggest a clear association between MDC infiltration and endothelial activation which in turn may contribute to damage of the blood brain barrier integrity. The recruitment of monocytes could be a consequence rather than the cause of the severity of the disease. Whether monocyte infiltration is beneficial or detrimental to AD pathology remains to be fully elucidated. These findings open the opportunity to design targeted therapies, not only for microglia but also for the peripheral immune cell population to modulate amyloid pathology and provide a better understanding of the immunological mechanisms underlying the progression of AD.

Dataset Information

Hypertension drives parenchymal ?-amyloid accumulation in the brain parenchyma.

Publications

Hypertension drives parenchymal β-amyloid accumulation in the brain parenchyma.

Similar Datasets

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