Cortical microinfarcts (CMIs) observed in brains of patients with Alzheimer’s disease tend to be located close to vessels afflicted with cerebral amyloid angiopathy (CAA). CMIs in Alzheimer’s disease are preferentially distributed in the arterial borderzone, an area most vulnerable to hypoperfusion. However, the causal association between CAA and CMIs remains to be elucidated. This study consists of two parts: (1) an observational study using postmortem human brains (n = 31) to determine the association between CAA and CMIs, and (2) an experimental study to determine whether hypoperfusion worsens CAA and induces CMIs in a CAA mouse model. In postmortem human brains, the density of CMIs was 0.113/cm2 in mild, 0.584/cm2 in moderate, and 4.370/cm2 in severe CAA groups with a positive linear correlation (r = 0.6736, p < 0.0001). Multivariate analysis revealed that, among seven variables (age, disease, senile plaques, neurofibrillary tangles, CAA, atherosclerosis and white matter damage), only the severity of CAA was a significant multivariate predictor of CMIs (p = 0.0022). Consistent with the data from human brains, CAA model mice following chronic cerebral hypoperfusion due to bilateral common carotid artery stenosis induced with 0.18-mm diameter microcoils showed accelerated deposition of leptomeningeal amyloid β (Aβ) with a subset of them developing microinfarcts. In contrast, the CAA mice without hypoperfusion exhibited very few leptomeningeal Aβ depositions and no microinfarcts by 32 weeks of age. Following 12 weeks of hypoperfusion, cerebral blood flow decreased by 26% in CAA mice and by 15% in wild-type mice, suggesting impaired microvascular function due to perivascular Aβ accumulation after hypoperfusion. Our results suggest that cerebral hypoperfusion accelerates CAA, and thus promotes CMIs.Electronic supplementary materialThe online version of this article (doi:10.1007/s00401-011-0925-9) contains supplementary material, which is available to authorized users.

No abstract

Diffuse serotonergic fibers are presumed to project to the telencephalon from the nucleus raphe dorsalis (NRD) of the midbrain, in a manner similar to the cholinergic projections from the nucleus basalis of Meynert (nbM) to the cerebral cortex. Neuropathological changes in both of these nuclei have been reported in Alzheimer's disease (AD). Although many morphometric studies of the nbM in AD have been documented, only one such study of the NRD has been conducted so far; it demonstrated a sixfold increase in neurofibrillary tangles in AD but no statistically significant difference in the number of neurons in patients with AD and age-matched controls. A study of the NRD utilizing different stains and wider anatomical boundaries is detailed in this report of 5 patients with AD and 7 age-matched controls. In AD the NRD showed 39 times more neurofibrillary tangles and the number and cell density of large neurons were reduced to 23% and 28%, respectively, of those in the controls. A small number of senile plaques were found in the NRD in all patients with AD but none were found in the controls.

No abstract

• This study tested the validity of noninvasive electrical conductivity measurements by MRI. • This study also evaluated the electrical conductivity characteristics of diffuse glioma. • Gliomas have higher electrical conductivity values than the normal brain parenchyma. • Noninvasive electrical conductivity measurement can be helpful for better characterisation of glioma.

The m-CT value of GGO lesions is a risk factor associated with their future change. The interval of follow-up CT scanning or treatment policy should be determined considering the m-CT value.

Background: Although the clinical significance of so-called microbleeds (MBs) in gradient-echo MR images (GRE-MRI) has been extensively researched, the histopathological evaluation is notably insufficient. Methods: Postmortem GRE-MRI was obtained of water-immersed formalin-fixed tissue blocks from a 97-year-old hypertensive woman with 9 antemortem MBs. Histologic slides were compared with those of MRI. Results: Microscopic examination revealed clusters of hemosiderin-laden macrophages in 8 MBs and arteriolar pseudocalcification in 1 MB in the left pallidum. Hypertensive microangiopathies were found in 5 lesions. The sizes of the lesions with hemosiderin deposits were roughly comparable with the MBs of GRE-MRI. Conclusions: All of the MBs but for 1 exception were proved to be hemosiderin deposits and frequently associated with hypertensive microangiopathy.

The pathogenesis of HDLS seems to be associated with microglial vulnerability and morphological alterations. Ann Neurol 2016;80:554-565.