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Abstract Cerebral white matter rarefaction (CWMR) was considered by Binswanger and Alzheimer to be due to cerebral arteriolosclerosis. Renewed attention came with CT and MR brain imaging, and neuropathological studies finding a high rate of CWMR in Alzheimer disease (AD). The relative contributions of cerebrovascular disease and AD to CWMR are still uncertain. In 1181 autopsies by the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND), large-format brain sections were used to grade CWMR and determine its vascular and neurodegenerative correlates. Almost all neurodegenerative diseases had more severe CWMR than the normal control group. Multivariable logistic regression models indicated that Braak neurofibrillary stage was the strongest predictor of CWMR, with additional independently significant predictors including age, cortical and diencephalic lacunar and microinfarcts, body mass index, and female sex. It appears that while AD and cerebrovascular pathology may be additive in causing CWMR, both may be solely capable of this. The typical periventricular pattern suggests that CWMR is primarily a distal axonopathy caused by dysfunction of the cell bodies of long-association corticocortical projection neurons. A consequence of these findings is that CWMR should not be viewed simply as “small vessel disease” or as a pathognomonic indicator of vascular cognitive impairment or vascular dementia.

The determination of RNA integrity is a critical quality assessment tool for gene expression studies where the experiment’s success is highly dependent on the sample quality. Since its introduction in 1999, the gold standard in the scientific community has been the Agilent 2100 Bioanalyzer’s RNA integrity number (RIN), which uses a 1–10 value system, from 1 being the most degraded, to 10 being the most intact. In 2015, Agilent launched 4200 TapeStation’s RIN equivalent, and reported a strong correlation of r2 of 0.936 and a median error < ±0.4 RIN units. To evaluate this claim, we compared the Agilent 4200 TapeStation’s RIN equivalent (RINe) and DV200 to the Agilent 2100 Bioanalyzer’s RIN for 183 parallel RNA samples. In our study, using RNA from a total of 183 human postmortem brain samples, we found that the RIN and RINe values only weakly correlate, with an r2 of 0.393 and an average difference of 3.2 RIN units. DV200 also only weakly correlated with RIN (r2 of 0.182) and RINe (r2 of 0.347). Finally, when applying a cut-off value of 6.5 for both metrics, we found that 95.6% of samples passed with RIN, while only 23.5% passed with RINe. Our results suggest that even though RIN (Bioanalyzer) and RINe (TapeStation) use the same 1–10 value system, they should not be used interchangeably, and cut-off values should be calculated independently.

Astrocytes have multiple crucial roles, including maintaining brain homeostasis and synaptic function, performing phagocytic clearance, and responding to injury and repair. It has been suggested that astrocyte performance is progressively impaired with aging, leading to imbalances in the brain’s internal milieu that eventually impact neuronal function and lead to neurodegeneration. Until now, most evidence of astrocytic dysfunction in aging has come from experiments done with whole tissue homogenates, astrocytes collected by laser capture, or cell cultures derived from animal models or cell lines. In this study, we used postmortem-derived whole cells sorted with anti-GFAP antibodies to compare the unbiased, whole-transcriptomes of human astrocytes from control, older non-impaired individuals and subjects with different neurodegenerative diseases, such as Parkinson’s disease (PD), Alzheimer’s disease (ADD), and progressive supranuclear palsy (PSP). We found hundreds of dysregulated genes between disease and control astrocytes. In addition, we identified numerous genes shared between these common neurodegenerative disorders that are similarly dysregulated; in particular, UBC a gene for ubiquitin, which is a protein integral to cellular homeostasis and critically important in regulating function and outcomes of proteins under cellular stress, was upregulated in PSP, PD, and ADD when compared to control.

Abstract Brains of 42 COVID-19 decedents and 107 non-COVID-19 controls were studied. RT-PCR screening of 16 regions from 20 COVID-19 autopsies found SARS-CoV-2 E gene viral sequences in 7 regions (2.5% of 320 samples), concentrated in 4/20 subjects (20%). Additional screening of olfactory bulb (OB), amygdala (AMY) and entorhinal area for E, N1, N2, RNA-dependent RNA polymerase, and S gene sequences detected one or more of these in OB in 8/21 subjects (38%). It is uncertain whether these RNA sequences represent viable virus. Significant histopathology was limited to 2/42 cases (4.8%), one with a large acute cerebral infarct and one with hemorrhagic encephalitis. Case-control RNAseq in OB and AMY found more than 5000 and 700 differentially expressed genes, respectively, unrelated to RT-PCR results; these involved immune response, neuronal constituents, and olfactory/taste receptor genes. Olfactory marker protein-1 reduction indicated COVID-19-related loss of OB olfactory mucosa afferents. Iba-1-immunoreactive microglia had reduced area fractions in cerebellar cortex and AMY, and cytokine arrays showed generalized downregulation in AMY and upregulation in blood serum in COVID-19 cases. Although OB is a major brain portal for SARS-CoV-2, COVID-19 brain changes are more likely due to blood-borne immune mediators and trans-synaptic gene expression changes arising from OB deafferentation.

Background Hispanics seem to be at higher risk of developing Alzheimer's disease dementia (ADD) but there are few neuropathologically validated studies. Method The National Alzheimer's Coordinating Center (NACC) functions as the centralized data repository for the National Institute of Aging's (NIA's) Alzheimer's Disease Research Centers (ADRC) Program and currently hosts data from over 2,100 Hispanic participants who have donated their brains to the study, and close to 60% of those have had full neuropathological evaluations done at 28 different ADRCs. The main goal of this study is to compare the neuropathological changes observed in these subjects to those reported as non‐Hispanics. Result Hispanics in this study self‐identified as Caucasians (72%), African American (4%), Native American (less than 2.5%), or “Other Races or unknown” (20%), as compared to the non‐Hispanics, (82% Caucasian, 14% African American, 0.1% Other). The largest percentage of Hispanics were Mexican or of Mexican descent (64%), followed by 12% Puerto Rican, 6% Cuban, 5% Dominican, 6% South American, with the remainder from other central American countries or Spain. Sex distribution was similar in both groups with close to 49% of the participants identifying their biological sex as males. Hispanic participants died at younger ages (83 vs 84 years), had lower brain weights (1093 +/‐ 152g vs 1116 +/‐ 157g) and had a higher percentage of Intermediate to High levels of AD Neuropathological Changes (75% vs 67%). Vascular pathology was also more severe in Hispanics, both for moderate/severe cerebral amyloid angiopathy (45% to 29%) and moderate/severe cerebral white matter rarefaction (33% to 31%). Hispanics in this data set also had higher rates of heart attack, congestive heart failure, hypertension, and diabetes. Conclusion This also agrees with previous clinical studies suggesting that ethnic Hispanic people have greater white matter hyperintensity volumes and higher vascular risk factors, but additional studies are needed to also understand how race intersects ethnicity.

Hispanics seem to be at higher risk of developing Alzheimer's disease dementia (ADD) but there are few neuropathologically validated studies.BACKGROUNDHispanics seem to be at higher risk of developing Alzheimer's disease dementia (ADD) but there are few neuropathologically validated studies.The National Alzheimer's Coordinating Center (NACC) functions as the centralized data repository for the National Institute of Aging's (NIA's) Alzheimer's Disease Research Centers (ADRC) Program and currently hosts data from over 2,100 Hispanic participants who have donated their brains to the study, and close to 60% of those have had full neuropathological evaluations done at 28 different ADRCs. The main goal of this study is to compare the neuropathological changes observed in these subjects to those reported as non-Hispanics.METHODThe National Alzheimer's Coordinating Center (NACC) functions as the centralized data repository for the National Institute of Aging's (NIA's) Alzheimer's Disease Research Centers (ADRC) Program and currently hosts data from over 2,100 Hispanic participants who have donated their brains to the study, and close to 60% of those have had full neuropathological evaluations done at 28 different ADRCs. The main goal of this study is to compare the neuropathological changes observed in these subjects to those reported as non-Hispanics.Hispanics in this study self-identified as Caucasians (72%), African American (4%), Native American (less than 2.5%), or \"Other Races or unknown\" (20%), as compared to the non-Hispanics, (82% Caucasian, 14% African American, 0.1% Other). The largest percentage of Hispanics were Mexican or of Mexican descent (64%), followed by 12% Puerto Rican, 6% Cuban, 5% Dominican, 6% South American, with the remainder from other central American countries or Spain. Sex distribution was similar in both groups with close to 49% of the participants identifying their biological sex as males. Hispanic participants died at younger ages (83 vs 84 years), had lower brain weights (1093 +/- 152g vs 1116 +/- 157g) and had a higher percentage of Intermediate to High levels of AD Neuropathological Changes (75% vs 67%). Vascular pathology was also more severe in Hispanics, both for moderate/severe cerebral amyloid angiopathy (45% to 29%) and moderate/severe cerebral white matter rarefaction (33% to 31%). Hispanics in this data set also had higher rates of heart attack, congestive heart failure, hypertension, and diabetes.RESULTHispanics in this study self-identified as Caucasians (72%), African American (4%), Native American (less than 2.5%), or \"Other Races or unknown\" (20%), as compared to the non-Hispanics, (82% Caucasian, 14% African American, 0.1% Other). The largest percentage of Hispanics were Mexican or of Mexican descent (64%), followed by 12% Puerto Rican, 6% Cuban, 5% Dominican, 6% South American, with the remainder from other central American countries or Spain. Sex distribution was similar in both groups with close to 49% of the participants identifying their biological sex as males. Hispanic participants died at younger ages (83 vs 84 years), had lower brain weights (1093 +/- 152g vs 1116 +/- 157g) and had a higher percentage of Intermediate to High levels of AD Neuropathological Changes (75% vs 67%). Vascular pathology was also more severe in Hispanics, both for moderate/severe cerebral amyloid angiopathy (45% to 29%) and moderate/severe cerebral white matter rarefaction (33% to 31%). Hispanics in this data set also had higher rates of heart attack, congestive heart failure, hypertension, and diabetes.This also agrees with previous clinical studies suggesting that ethnic Hispanic people have greater white matter hyperintensity volumes and higher vascular risk factors, but additional studies are needed to also understand how race intersects ethnicity.CONCLUSIONThis also agrees with previous clinical studies suggesting that ethnic Hispanic people have greater white matter hyperintensity volumes and higher vascular risk factors, but additional studies are needed to also understand how race intersects ethnicity.