Predicting Post-Mortem α-Synuclein Pathology by the Combined Presence of Probable REM sleep behavior disorder and Hyposmia.

Background: Idiopathic rapid eye movement sleep behavior disorder (RBD) is a strong known predictor of a final clinicopathological diagnosis of a Lewy type α-synucleinopathy (LTS). Olfactory dysfunction is an early symptom of synucleinopathies and has been repeatedly associated with the presence of post-mortem LTS.

Objective: To assess the combined value of a clinician diagnosis of probable RBD (PRBD) and hyposmia in predicting the post-mortem presence of LTS in a broader, less-selected, volunteer elderly population.

Clinicopathological Heterogeneity of Lewy Body Diseases: The Profound Influence of Comorbid Alzheimer's Disease.

In recent years, proposals have been advanced to redefine or reclassify Lewy body disorders by merging the long-established entities of Parkinson's disease (PD), Parkinson's disease dementia (PDD) and dementia with Lewy bodies (DLB). These proposals reject the International DLB Consortium classification system that has evolved over three decades of consensus collaborations between neurologists, neuropsychologists and neuropathologists. While the Consortium's "one year rule" for separating PD and DLB has been criticized as arbitrary, it has been a pragmatic and effective tool for splitting the continuum between the two entities.

Parkinson's Disease Associated with G2019S LRRK2 Mutations without Lewy Body Pathology.

Background: The G2019S leucine-rich repeat kinase 2 (LRRK2) gene mutation is an important and commonly found genetic determinant of Parkinson's disease (PD). The neuropathological findings associated with this mutation have thus far been varied but are most often associated with Lewy body (LB) pathology.

Objective: Describe a case of clinical Parkinson's disease with levodopa responsiveness found to have LRRK2 mutations and the absence of Lewy bodies.

RNA sequencing of olfactory bulb in Parkinson's disease reveals gene alterations associated with olfactory dysfunction.

The olfactory bulb is involved early in the pathophysiology of Parkinson's disease (PD), which is consistent with the early onset of olfactory dysfunction. Identifying the molecular mechanisms through which PD affects the olfactory bulb could lead to a better understanding of the pathophysiology and etiology of olfactory dysfunction in PD. We specifically aimed to assess gene expression changes, affected pathways and co-expression network by whole transcriptomic profiling of the olfactory bulb in subjects with clinicopathologically defined PD.

Disease progression modelling reveals heterogeneity in trajectories of Lewy-type α-synuclein pathology.

Lewy body (LB) disorders, characterized by the aggregation of misfolded α-synuclein proteins, exhibit notable clinical heterogeneity. This may be due to variations in accumulation patterns of LB neuropathology. By applying data-driven disease progression modelling to regional neuropathological LB density scores from 814 brain donors, we describe three inferred trajectories of LB pathology that were characterized by differing clinicopathological presentation and longitudinal antemortem clinical progression.

Measuring Up: A Comparison of TapeStation 4200 and Bioanalyzer 2100 as Measurement Tools for RNA Quality in Postmortem Human Brain Samples.

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 r of 0.

Measuring up: A Comparison of Tapestation 4200 and Bioanalyzer 2100 as Measurement Tools for RNA Quality in Postmortem Human Brain Samples.

Determining RNA integrity is a critical quality assessment tool for gene expression studies where the experiment's success is highly dependent on 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 with 1 being the most degraded to 10 being the most intact. In 2015, Agilent launched the 4200 Tapestation's RIN equivalent and reported a strong correlation of r of 0.

The role of sex differences in depression in pathologically defined Alzheimer's disease.

Introduction: Sex differences in Alzheimer's disease (AD) may contribute to disease heterogeneity and affect prevalence, risk factors, disease trajectories and outcomes. Depression impacts a large number of patients with AD and has been reported to be more prevalent in women. We aimed to better understand the interaction between sex, depression and AD neuropathology, which could have implications for detection of symptoms, earlier diagnosis, therapeutic management, and enhanced quality of life.

Cerebral white matter rarefaction has both neurodegenerative and vascular causes and may primarily be a distal axonopathy.

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.

Low clinical sensitivity and unexpectedly high incidence for neuropathologically diagnosed progressive supranuclear palsy.

The objective of this study was to determine the prevalence, incidence, and clinical diagnostic accuracy for neuropathologically diagnosed progressive supranuclear palsy (PSP) with data from a longitudinal clinicopathological study using Rainwater criteria to define neuropathological PSP. Of 954 autopsy cases, 101 met Rainwater criteria for the neuropathologic diagnosis of PSP. Of these, 87 were termed clinicopathological PSP as they also had either dementia or parkinsonism or both.

Postmortem Cerebellar Volume Is Not Reduced in Essential Tremor: A Comparison with Multiple System Atrophy and Controls.

Background: Essential tremor (ET) is a common movement disorder in which cerebellar microscopic and volume alterations have been repeatedly reported although with disagreement between studies. However, pronounced heterogeneity was found with regard to cerebellar volume alterations.

Objective: This study aimed to assess postmortem cerebellar volume in subjects with or without ET, as compared with subjects with multiple system atrophy (MSA), a well-established cerebellar neurodegeneration.

SARS-CoV-2 Brain Regional Detection, Histopathology, Gene Expression, and Immunomodulatory Changes in Decedents with COVID-19.

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%).

Olfactory Bulb Amyloid-β Correlates With Brain Thal Amyloid Phase and Severity of Cognitive Impairment.

The Alzheimer disease (AD) neuropathological hallmarks amyloid β (Aβ) and tau neurofibrillary (NF) pathology have been reported in the olfactory bulb (OB) in aging and in different neurodegenerative diseases, which coincides with frequently reported olfactory dysfunction in these conditions. To better understand when the OB is affected in relation to the hierarchical progression of Aβ throughout the brain and whether OB pathology might be an indicator of AD severity, we assessed the presence of OB Aβ and tau NF pathology in an autopsy cohort of 158 non demented control and 173 AD dementia cases. OB Aβ was found in less than 5% of cases in lower Thal phases 0 and 1, in 20% of cases in phase 2, in 60% of cases in phase 3 and in more than 80% of cases in higher Thal phases 4 and 5.

Effect of olfactory bulb pathology on olfactory function in normal aging.

Decline of olfactory function is frequently observed in aging and is an early symptom of neurodegenerative diseases. As the olfactory bulb (OB) is one of the first regions involved by pathology and may represent an early disease stage, we specifically aimed to evaluate the contribution of OB pathology to olfactory decline in cognitively normal aged individuals without parkinsonism or dementia. This clinicopathological study correlates OB tau, amyloid β (Aβ) and α-synuclein (αSyn) pathology densities and whole brain pathology load to olfactory identification function as measured with the University of Pennsylvania Smell Identification Test (UPSIT) and clinical data measured proximate to death in a large autopsy study including 138 cases considered non-demented controls during life.

Hemispheric Asymmetry and Atypical Lobar Progression of Alzheimer-Type Tauopathy.

The spread of neurofibrillary tau pathology in Alzheimer disease (AD) mostly follows a stereotypical pattern of topographical progression but atypical patterns associated with interhemispheric asymmetry have been described. Because histopathological studies that used bilateral sampling are limited, this study aimed to assess interhemispheric tau pathology differences and the presence of topographically atypical cortical spreading patterns. Immunohistochemical staining for detection of tau pathology was performed in 23 regions of interest in 57 autopsy cases comparing bilateral cortical regions and hemispheres.

Olfactory-Trigeminal Interactions in Patients with Parkinson's Disease.

Olfactory dysfunction (OD) is a highly frequent early non-motor symptom of Parkinson's disease (PD). An important step to potentially use OD for the development of early diagnostic tools of PD is to differentiate PD-related OD from other forms of non-parkinsonian OD (NPOD: postviral, sinunasal, post-traumatic, and idiopathic OD). Measuring non-olfactory chemosensory modalities, especially the trigeminal system, may allow to characterize a PD-specific olfactory profile.

Olfactory bulb surroundings can help to distinguish Parkinson's disease from non-parkinsonian olfactory dysfunction.

Background: The olfactory bulb is one of the first regions of insult in Parkinson's disease (PD), consistent with the early onset of olfactory dysfunction. Investigations of the olfactory bulb may, therefore, help early pre-motor diagnosis. We aimed to investigate olfactory bulb and its surrounding regions in PD-related olfactory dysfunction when specifically compared to other forms of non-parkinsonian olfactory dysfunction (NPOD) and healthy controls.

Parkinson's Disease Affects Functional Connectivity within the Olfactory-Trigeminal Network.

Background: Olfactory dysfunction (OD) is a frequent symptom of Parkinson's disease (PD) that appears years prior to diagnosis. Previous studies suggest that PD-related OD is different from non-parkinsonian forms of olfactory dysfunction (NPOD) as PD patients maintain trigeminal sensitivity as opposed to patients with NPOD who typically exhibit reduced trigeminal sensitivity. We hypothesize the presence of a specific alteration of functional connectivity between trigeminal and olfactory processing areas in PD.

Orthonasal, but not Retronasal Olfaction Is Specifically Impaired in Parkinson's Disease.

Olfactory dysfunction (OD) in Parkinson's disease (PD) appears several years before the presence of motor disturbance. Olfactory testing has the potential to serve as a tool for early detection of PD, but OD is not specific to PD as it affects up to 20% of the general population. Olfaction includes an orthonasal and a retronasal components; in some forms of OD, retronasal olfactory function is preserved.

Specific intranasal and central trigeminal electrophysiological responses in Parkinson's disease.

Olfactory dysfunction is a frequent early non-motor symptom of Parkinson's disease (PD). There is evidence that with regard to trigeminal perception, PD-related olfactory dysfunction is different from other olfactory disorders. More specifically, trigeminal sensitivity, when measured behaviorally, was unimpaired in PD patients as opposed to patients with non-Parkinsonian olfactory dysfunction (NPOD).

Chemosensory perception is specifically impaired in Parkinson's disease.

Patients with Parkinson's Disease (PD) exhibit a considerably diminished sense of smell. The olfactory system is intimately connected to the trigeminal system, responsible for the perception of sensations such as freshness, warmth or piquancy in odorants. Usually, olfactory impairment is associated with a similar reduction of trigeminal sensitivity.