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Dementia is the clinical consequence of various neurological disorders with a multitude of etiologies. Precise knowledge of the underlying pathologies is essential for an accurate treatment of patients and for the development of suitable disease biomarkers. A definite diagnosis of many of the disorders, particularly for neurodegenerative ones, can only be made after a thorough postmortem neuropathological examination. This highlights the importance of performing a brain autopsy and the relevance of a close interaction between clinicians, neuroimaging disciplines and neuropathologists as well as with basic researchers. This article aims to give a brief overview on the neuropathology of dementia focusing on neurodegenerative diseases, to further facilitate interdisciplinary collaboration., (© 2021. The Author(s).)

The objective of this work is to describe the neuropathological findings of a patient clinically presenting with rapidly progressive nonspecific neurological symptoms suggestive of Creutzfeldt-Jakob disease. Methods used were clinical description with laboratory analyses, repeated electroencephalogram, cerebral computed tomography, magnetic resonance imaging studies and details on neuropathological work-up. Neuropathological examination excluded Creutzfeldt-Jakob disease. By contrast other neurodegenerative changes combining Alzheimer-type pathology and Lewy body pathology were detected as the most likely substrate of neurological symptoms. Dementia with Lewy bodies should be included in the differential diagnosis in individuals presenting with rapidly progressive dementia.

Here, we summarise the results after carrying out a large survey regarding the assessment of vascular alterations, both vessel changes and vascular lesions in an inter-laboratory setting. In total, 32 neuropathologists from 22 centres, most being members of BrainNet Europe (BNE), participated by filling out a questionnaire with emphasis on assessment of common vascular alterations seen in the brains of aged subjects. A certain level of harmonisation has been reached among BNE members regarding sectioning of the brain, harvesting of brain tissue for histology and staining used when compared to the survey carried out in 2006 by Pantoni and colleagues. The most significant variability was seen regarding the assessment of severity and of clinical significance of vascular alterations. Two strategies have recently been recommended regarding the assessment of vascular alterations in aged and demented subjects. The National Institute on Aging - Alzheimer's Association (NIA-AA) recommends the assessment of hippocampal sclerosis, vascular brain injury and microvascular lesions in 12 regions. Although this strategy will be easy to follow, the recommendations do not inform how the load of observed alterations should be assessed and when the observed lesions are of significance. Deramecourt and his colleagues recommend an assessment and semiquantitative grading of various pathologies in 4 brain regions. This strategy yielded a total score of 0 to 20 as an estimate of pathology load. It is, however, not clear which score is considered to be of clinical significance. Furthermore, in several BNE trials the semiquantitative assessment has yielded poor agreement rates; an observation that might negatively influence the strategy proposed by Deramecourt and his colleagues. In line with NIA-AA, a dichotomised approach of easily recognisable lesions in a standardised set of brain regions harvested for neuropathological assessment and applying reproducible sampling and staining strategies is recommended by BNE. However, a simple strategy regarding assessment of load of alteration is urgently needed to yield reproducible, and at the same time, comparable results between centres., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Frontotemporal lobar degenerations are a group of disorders characterized by circumscribed degeneration of the frontal and temporal lobes and diverse histopathologic features. We report clinical, neuropathologic, ultrastructural, biochemical, and genetic data on 7 individuals with a 4-repeat tauopathy characterized by the presence of globular glial inclusions (GGIs) in brain white matter. Clinical manifestations were compatible with the behavioral variant of frontotemporal dementia and included motor neuron symptoms; there was prominent neuronal loss in the frontal and temporal cortex, subiculum, and amygdala. The surrounding white matter showed abundant GGIs composed of abnormal filaments present mostly in oligodendrocytes. The severity of white matter tau abnormalities correlated with a reduction in myelin and axons and with microglial activation. Western blotting of sarkosyl-insoluble tau demonstrated the presence of 2 major tau bands of 64 and 68 kd. No mutations in the microtubule-associated protein tau gene were detected in 2 affected individuals. We propose that 4-repeat tau-immunoreactive GGIs are the neuropathologic hallmark of a distinct sporadic tauopathy with variable clinical presentations that include frontotemporal dementia and occasionally upper motor neuron disease. This type of tauopathy with GGIs expands the group of neurodegenerativedisorders in which oligodendroglial pathology predominates, beyond the synucleinopathy multiple system atrophy disorders.

Background: Dementia results from heterogeneous diseases of the brain. Mixed disease forms are increasingly recognized., Methods: We performed a survey within brain banks of BrainNet Europe to estimate the proportion of mixed disease forms underlying dementia and age- and gender-specific influences., Results: Data collected in 9 centres from 3,303 individuals were analysed. The proportion of patients with mixed diagnoses among all cases with Alzheimer disease (AD), vascular pathology (VP), argyrophilic grain dementia (AGD), and synucleinopathies, such as Lewy body dementia (LBD), Parkinson disease (PD) and synuclein pathology only in the amygdala, was 53.3%. Mixed pathology was more frequently reported with LBD, PD, AGD, and VP than with AD. The percentage of mixed diagnoses for AGD and VP significantly differed between centres. In patients younger than 75 years, synucleinopathies, and pure forms of AD, VP, and AGD were more frequent in men. Above 75 years of age, more women had pure AD and pure AGD., Conclusions: The most obvious neuropathological alteration should not terminate the diagnostic procedure since copathology is likely to be found. Neuropathological interpretation of AGD and VP has not been sufficiently established in a consensus. Pure forms of synucleinopathies are unlikely sole substrates for dementia., (Copyright 2008 S. Karger AG, Basel.)

Background and purpose: Argyrophilic grain disease (AGD) is a limbic‐predominant 4R‐tauopathy. AGD is thought to be an age‐related disorder and is frequently detected as a concomitant pathology with other neurodegenerative conditions. There is a paucity of data on the clinical phenotype of pure AGD. In elderly patients, however, AGD pathology frequently associates with cognitive decline, personality changes, urine incontinence and cachexia. In this study, clinicopathological findings were analysed in individuals younger than 75. Methods: Patients were identified retrospectively based on neuropathological examinations during 2006–2017 and selected when AGD was the primary and dominant pathological finding. Clinical data were obtained retrospectively through medical records. Results: In all, 55 patients (2% of all examinations performed during that period) with AGD were identified. In seven cases (13%) AGD was the primary neuropathological diagnosis without significant concomitant pathologies. Two patients were female, median age at the time of death was 64 years (range 51–74) and the median duration of disease was 3 months (range 0.5–36). The most frequent symptoms were progressive cognitive decline, urinary incontinence, seizures and psychiatric symptoms. Brain magnetic resonance imaging revealed mild temporal atrophy. Conclusions: Argyrophilic grain disease is a rarely recognized limbic tauopathy in younger individuals. Widening the clinicopathological spectrum of tauopathies may allow identification of further patients who could benefit from tau‐based therapeutic strategies. [ABSTRACT FROM AUTHOR]

The article presents a neuropathological study of a 60-year-old man with frontotemporal lobar degenerations (FTLD) to determine the correlation of TARDBP mutation p.Ile383Val with semantic dementia and complex proteinopathy. The study investigates the temporally accentuated atrophy. The study concludes that the presence of p.Ile383Val mutation in TARDBP indicates a complex clinico-genetic-neuropathological relationships within the continuum FTLD-amyotrophic lateral sclerosis (ALS).