Predictors of cognitive impairment in primary age-related tauopathy: an autopsy study.

Primary age-related tauopathy (PART) is a form of Alzheimer-type neurofibrillary degeneration occurring in the absence of amyloid-beta (Aβ) plaques. While PART shares some features with Alzheimer disease (AD), such as progressive accumulation of neurofibrillary tangle pathology in the medial temporal lobe and other brain regions, it does not progress extensively to neocortical regions. Given this restricted pathoanatomical pattern and variable symptomatology, there is a need to reexamine and improve upon how PART is neuropathologically assessed and staged.

Single-nucleus transcriptome analysis of human brain immune response in patients with severe COVID-19.

Background: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, has been associated with neurological and neuropsychiatric illness in many individuals. We sought to further our understanding of the relationship between brain tropism, neuro-inflammation, and host immune response in acute COVID-19 cases.

Methods: Three brain regions (dorsolateral prefrontal cortex, medulla oblongata, and choroid plexus) from 5 patients with severe COVID-19 and 4 controls were examined.

Progressive Multifocal Leukoencephalopathy in a Patient With Progressive Multiple Sclerosis Treated With Ocrelizumab Monotherapy.

Importance: Progressive multifocal leukoencephalopathy (PML) is an opportunistic infection caused by the JC virus that has no proven effective treatment. Although rare cases of PML have occurred with other anti-CD20 therapies, there had been no prior cases associated with ocrelizumab.

Objective: To report the first ever case of PML occurring with ocrelizumab monotherapy in a patient with progressive multiple sclerosis without prior immunomodulation.

Early Selective Vulnerability of the CA2 Hippocampal Subfield in Primary Age-Related Tauopathy.

Primary age-related tauopathy (PART) is a neurodegenerative entity defined as Alzheimer-type neurofibrillary degeneration primarily affecting the medial temporal lobe with minimal to absent amyloid-β (Aβ) plaque deposition. The extent to which PART can be differentiated pathoanatomically from Alzheimer disease (AD) is unclear. Here, we examined the regional distribution of tau pathology in a large cohort of postmortem brains (n = 914).

Molecular abnormalities in autopsied brain tissue from the inferior horn of the lateral ventricles of nonagenarians and Alzheimer disease patients.

Background: The ventricular system plays a vital role in blood-cerebrospinal fluid (CSF) exchange and interstitial fluid-CSF drainage pathways. CSF is formed in the specialized secretory tissue called the choroid plexus, which consists of epithelial cells, fenestrated capillaries and the highly vascularized stroma. Very little is currently known about the role played by the ventricles and the choroid plexus tissue in aging and Alzheimer's disease (AD).

Artificial intelligence in neuropathology: deep learning-based assessment of tauopathy.

Accumulation of abnormal tau in neurofibrillary tangles (NFT) occurs in Alzheimer disease (AD) and a spectrum of tauopathies. These tauopathies have diverse and overlapping morphological phenotypes that obscure classification and quantitative assessments. Recently, powerful machine learning-based approaches have emerged, allowing the recognition and quantification of pathological changes from digital images.

Localized cortical chronic traumatic encephalopathy pathology after single, severe axonal injury in human brain.

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with repetitive mild impact traumatic brain injury from contact sports. Recently, a consensus panel defined the pathognomonic lesion for CTE as accumulations of abnormally hyperphosphorylated tau (p-tau) in neurons (neurofibrillary tangles), astrocytes and cell processes distributed around small blood vessels at sulcal depths in irregular patterns within the cortex. The pathophysiological mechanism for this lesion is unknown.

The triggering receptor expressed on myeloid cells 2 (TREM2) is associated with enhanced inflammation, neuropathological lesions and increased risk for Alzheimer's dementia.

Introduction: The objective of this study was to elucidate the relationship between the triggering receptor expressed on myeloid cells 2 (TREM2) risk variant, neuropathological lesions, alterations in gene and protein expression, and the severity of neuroinflammation.

Methods: The genetic association study of the R47 H TREM2 variant with Alzheimer's disease (AD), neuropathology, and changes in TREM2 and TYRO protein tyrosine kinase-binding protein (TYROBP) gene and protein expression, and neuroinflammatory markers.

Results: The TREM2 variant is associated with: (i) AD (odds ratio: 4.

Cell cycle checkpoint abnormalities during dementia: A plausible association with the loss of protection against oxidative stress in Alzheimer's disease [corrected].

Background: Increasing evidence suggests an association between neuronal cell cycle (CCL) events and the processes that underlie neurodegeneration in Alzheimer's disease (AD). Elevated levels of oxidative stress markers and mitochondrial dysfunction are also among early events in AD. Recent studies have reported the role of CCL checkpoint proteins and tumor suppressors, such as ATM and p53 in the control of glycolysis and oxidative metabolism in cancer, but their involvement in AD remains uncertain.

Corticosteroids, but not NSAIDs, are associated with less Alzheimer neuropathology.

The objective of this study was to test the hypothesis that corticosteroid and nonsteroidal anti-inflammatory drug (NSAID) medications are associated with less global and regional Alzheimer's disease (AD) neuropathology. This postmortem study was based on 694 brains of subjects from the Mount Sinai School of Medicine Brain Bank who did not have neuropathologies other than neuritic plaques (NPs), neurofibrillary tangles (NFTs), or cerebrovascular disease. Densities of NPs and of NFTs were assessed in several neocortical regions and in the hippocampus, entorhinal cortex, and amygdala.

Synthesis and antimicrobial activity of some new 1,3,4-thiadiazoles and 1,3,4-thiadiazines containing 1,2,4-Triazolo nucleus.

The desired fused ring system 3-(3-chlorophenyl)-6-aryl-5,6-dihydro[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles 5a-j were synthesized by the reaction of 4-amino-5-(3-chlorophenyl)-4H-1,2,4-triazole-3-thiol and different aryl aldehydes in the presence of catalytic amount of p-TsOH in dry DMF, while 3-(3-chlorophenyl)-6-aryl-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazines 7a-j were synthesized by using 4-amino-5-(3-chlorophenyl)-4H-1,2,4-triazole-3-thiol and different phenacyl bromides in dry methanol. Their IR, 1H NMR, mass spectral data and elemental analyses were in accord with assigned structures. All the newly synthesized compounds were screened for their antimicrobial activity.

Profiles of Alzheimer's disease-related pathology in an aging urban population sample in India.

Systematic studies on Alzheimer's disease (AD)-related pathology that complement clinical and epidemiological data on dementia from low and middle income countries are rare. We report the first large study on AD-related pathology in autopsy service-derived brains from an urban center in India, a low/middle income country, and compare findings with a similar sample from New York. Amyloid-β plaques and neurofibrillary tangles were assessed in 91 brain specimens derived from hospital autopsy cases from Mumbai, India (age 60+ years; mean age 71.

Cortical neuritic plaques and hippocampal neurofibrillary tangles are related to dementia severity in elderly schizophrenia patients.

Cognitive decline has been described in elderly patients with schizophrenia, but the underlying pathology remains unknown. Some studies report increases in plaques and neurofibrillary tangles, but there is no evidence for an increased risk for Alzheimer's disease (AD) in elderly schizophrenics. Models of a decreased cerebral reserve suggest that increases in AD-related neuropathology below the threshold for a neuropathological diagnosis could be related to dementia severity in elderly schizophrenia patients.

Parkinson's disease dementia: a diminished role for the Lewy body.

The literature currently views Lewy bodies as central in the pathogenesis of Parkinson's disease dementia (PDD) when Alzheimer's disease (AD) or vascular pathology is not present. Because the neuropathology of PDD is not well understood, the pathological features of PDD were characterized in eighteen PD brain specimens using published criteria for AD, Diffuse Lewy Body Disease (DLBD), and Vascular Disease as a framework. Among the PD dementia (n=16) subjects, 3 (19%) did not have LBs outside of the brain stem, nor AD or vascular pathology.

Serum lipids are related to Alzheimer's pathology in nursing home residents.

Background: Studies of associations between serum lipids and Alzheimer's disease (AD) or other dementias in the elderly show conflicting results, perhaps due to misclassification of the various dementias.

Methods: For 358 nursing home residents, serum lipids were studied at admission and diagnoses established at autopsy. We used defined neuropathological criteria to distinguish the presence of AD and to avoid errors of clinical dementia assessment.

Role of the neuropathology of Alzheimer disease in dementia in the oldest-old.

Background: Neuritic plaques (NPs) and neurofibrillary tangles (NFTs) in the brain, especially in the hippocampus, entorhinal cortex, and isocortex, are hallmark lesions of Alzheimer disease and dementia in the elderly. However, this association has not been extensively studied in the rapidly growing population of the very old.

Objective: To assess the relationship between estimates of cognitive function and NP and NFT pathologic conditions in 317 autopsied persons aged 60 to 107 years.

Clinical dementia rating performed several years prior to death predicts regional Alzheimer's neuropathology.

Aims: To assess the relationships between early and late antemortem measures of dementia severity and Alzheimer disease (AD) neuropathology severity.

Methods: 40 residents of a nursing home, average age at death 82.0, participated in this longitudinal cohort study with postmortem assessment.

Increased neurofibrillary tangles in patients with Alzheimer disease with comorbid depression.

Objective: Recent evidence suggests that a history of major depression may lead to increases in hippocampal neuropathology in Alzheimer disease (AD). The authors tested the hypothesis that neuritic plaques and neurofibrillary tangles are more pronounced in the brains of patients with AD with comorbid depression as compared with patients with AD without depression.

Methods: Brain samples from patients were selected from the U.

Number of children is associated with neuropathology of Alzheimer's disease in women.

Objective: To examine the association between number of born children and neuropathology of Alzheimer's disease (AD).

Methods: The brains of 86 subjects with data on the number of biological children born, were studied postmortem. Primary analyses included 73 subjects (average age at death=80; 42 women) devoid of cerebrovascular disease associated lesions (i.

Pituicytoma presenting with spontaneous hemorrhage.

Pituicytomas are rare tumors. Previously reported pituicytomas all presented with signs and symptoms relating to mass effect or endocrinological dysfunction. We report a 47 year old man who presented with sudden, severe headache and was found to have a hemorrhagic suprasellar mass with hemorrhage into the third ventricle.

Increased hippocampal plaques and tangles in patients with Alzheimer disease with a lifetime history of major depression.

Context: The hallmark pathological changes in Alzheimer disease (AD) are abundant plaque and tangle formation, especially in the temporal lobes and hippocampus. Although there is increasing evidence that major depression may interact with neuropathological processes in AD, there have been no studies of neuropathological changes in AD as a function of history of major depression.

Objective: To test the hypothesis that neuritic plaques and neurofibrillary tangles are more pronounced in the hippocampus of patients with AD with a lifetime history of major depressive disorder, as compared with patients with AD without depression history.

Type 2 diabetes is negatively associated with Alzheimer's disease neuropathology.

Background: In cross-sectional and longitudinal studies, type 2 diabetes has been positively associated with the risk of Alzheimer's disease (AD). The present descriptive study compared diabetic and nondiabetic subjects on the severity of neuritic plaques and neurofibrillary tangles (NFTs) in the cerebral cortex and in the hippocampus.

Methods: The study included specimens from 385 consecutive autopsies of residents of a nursing home (15.

Parkinson's disease without expected neuropathologic abnormality.

A case is reported of an initially 78-year-old man whose presentation and course, closely followed over 10 years by an academic neurologist, were consistent with classic idiopathic Parkinson's disease (PD), including unilateral onset, obvious cogwheeling, and a very good prolonged response to levodopa/carbidopa (LD/CD). Yet at autopsy, there was no neuronal loss in the substantia nigra nor were there any Lewy bodies or immunochemical evidence of alpha synuclein in the multiple brain structures studied. This case does not support the hypothesis that the use of LD/CD is toxic to the substantia nigra in people.

Autonomic failure as the initial presentation of Parkinson disease and dementia with Lewy bodies.

The authors report the clinical and postmortem neuropathologic findings of two patients, one with Parkinson disease (PD) and one with dementia with Lewy bodies (DLB), both of whom initially sought treatment for isolated autonomic failure. These cases suggest that neurodegeneration in PD and DLB may begin outside the CNS in autonomic postganglionic neurons, a finding with potential diagnostic and therapeutic implications.