Neuropathological findings in entorhinal cortex of subjects aged 50 years or older and their correlation with dementia in a sample from Southern Brazil

ABSTRACT Introduction: The aims of this study were to survey neurodegenerative changes detected by abnormal protein deposits in the Entorhinal Cortex (EC) of subjects aged 50 years or older and to correlate these findings with suspected dementia, as detected by the IQCODE (Informant Questionnaire on Cognitive Decline in the Elderly) . Methods: Fourteen brains were submitted to the immunohistochemistry technique for different proteins (beta-amyloid, tau, -synuclein and phospho-TDP-43) and data obtained compared with IQCODE scores. Results: Fifty-seven percent of the individuals exhibited IQCODE results compatible with dementia, being classified into the demented group (DG): 87.5% of patients had neuropathological findings corresponding to Alzheimer's-like brain pathology (ALBP). Of the patients in the non-demented group (NDG), 16.7% met neuropathological criteria for ALBP. All individuals in the DG showed deposits of more than one kind of protein in the EC. The most common association was hyperphosphorylated tau and beta-amyloid protein (87.5%). Discussion: Most individuals with dementia had neuropathological findings of ALBP, as did one individual with no signs of dementia, characterizing a preclinical stage. The results of this study suggest that deposits of a single type of anomalous protein are normal findings in an aging brain, while more than one kind of protein or the combined presence of anomalous protein deposits indicate the presence of dementia.

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3D printing of beta-amyloid protein deposits along capillary walls

Journal of Biomedical Graphics and Computing ◽

10.5430/jbgc.v7n1p8 ◽

2017 ◽

Vol 7 (1) ◽

pp. 8

Author(s):

China Blue ◽

Seth S. Horowitz ◽

Peter J. Snyder

Keyword(s):

3D Printing ◽

Laser Scanning ◽

Protein A ◽

Beta Amyloid ◽

Confocal Laser ◽

Amyloid Protein ◽

Root Cause ◽

Protein Deposits ◽

Beta Amyloid Protein ◽

Vessel Walls

Abnormally high levels of neocortical beta-amyloid protein (A+) reflect Alzheimer’s disease (AD) pathology in persons with clinical evidence of dementia or mild cognitive impairment (MCI). The abnormal aggregation of beta-amyloid protein in the brain neuropil may lead to either diffuse plaques and/or concentrated neuritic plaques, with the latter form of deposits often present in the vicinity of the cerebral microvasculature. The A protein, with its crystalline molecular structure, infiltrates the vessel walls and compromises the blood-brain barrier (BBB). The physical basis for this was elegantly shown by Meyer and colleagues, in a 2008 publication showing two-dimensional (2D) confocal laser scanning microscopic imaging of vascular A protein deposits in APP23 transgenic mice. These investigators showed accumulations of “tuft-life structures”, also referred to as “pompons” with protruding spikes on – and embedded within – microvessels. These pompons of beta-amyloid protein “consist of fibrillar structures, [and] can encircle and constrict capillaries, and are often associated with distortion of capillaries”.We were struck by both the heuristic value of the imaging of Meyer and colleagues, in explaining the root cause of both the amyloid-related alterations in the vascular bed, and depicting minute protein deposits that are both geometrically complex, seemingly delicate and fragile, and yet tenacious in their embedding within small vessel walls. We re-created these images with standard 3D printing technology (extruded plastic) for both educational/teaching and artistic purposes.

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Human kidney is a target for novel severe acute respiratory syndrome coronavirus 2 infection

Nature Communications ◽

10.1038/s41467-021-22781-1 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Bo Diao ◽

Chenhui Wang ◽

Rongshuai Wang ◽

Zeqing Feng ◽

Ji Zhang ◽

...

Keyword(s):

Severe Acute Respiratory Syndrome ◽

Kidney Injury ◽

Human Kidney ◽

The Elderly ◽

Tubular Damage ◽

Clinical Parameters ◽

Double Staining ◽

Protein Deposits ◽

Prostaglandin D Synthase

AbstractIt is unclear whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can directly infect human kidney, thus leading to acute kidney injury (AKI). Here, we perform a retrospective analysis of clinical parameters from 85 patients with laboratory-confirmed coronavirus disease 2019 (COVID-19); moreover, kidney histopathology from six additional COVID-19 patients with post-mortem examinations was performed. We find that 27% (23/85) of patients exhibited AKI. The elderly patients and cases with comorbidities (hypertension and heart failure) are more prone to develop AKI. Haematoxylin & eosin staining shows that the kidneys from COVID-19 autopsies have moderate to severe tubular damage. In situ hybridization assays illustrate that viral RNA accumulates in tubules. Immunohistochemistry shows nucleocapsid and spike protein deposits in the tubules, and immunofluorescence double staining shows that both antigens are restricted to the angiotensin converting enzyme-II-positive tubules. SARS-CoV-2 infection triggers the expression of hypoxic damage-associated molecules, including DP2 and prostaglandin D synthase in infected tubules. Moreover, it enhances CD68+ macrophages infiltration into the tubulointerstitium, and complement C5b-9 deposition on tubules is also observed. These results suggest that SARS-CoV-2 directly infects human kidney to mediate tubular pathogenesis and AKI.

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