Postmortem neuropathology in early Huntington disease.

Two aspects of the neuropathology of early Huntington disease (HD) are examined. Neurons of the neostriatum are counted to determine relative loss in striosomes versus matrix at early stages, including for the first time in preclinical cases. An immunohistochemical procedure is described that tentatively distinguishes early HD from HD mimic disorders in postmortem brains.

Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer's Disease.

To elucidate the role of Tau isoforms and post-translational modification (PTM) stoichiometry in Alzheimer's disease (AD), we generated a high-resolution quantitative proteomics map of 95 PTMs on multiple isoforms of Tau isolated from postmortem human tissue from 49 AD and 42 control subjects. Although Tau PTM maps reveal heterogeneity across subjects, a subset of PTMs display high occupancy and frequency for AD, suggesting importance in disease. Unsupervised analyses indicate that PTMs occur in an ordered manner, leading to Tau aggregation.

Publisher Correction: Enhancers active in dopamine neurons are a primary link between genetic variation and neuropsychiatric disease.

In the version of this article initially published, the legends for Supplementary Figs. 4-8 and 10-14 contained errors. The Supplementary Figure legends have been corrected in the HTML and PDF versions of the article.

Enhancers active in dopamine neurons are a primary link between genetic variation and neuropsychiatric disease.

Enhancers function as DNA logic gates and may control specialized functions of billions of neurons. Here we show a tailored program of noncoding genome elements active in situ in physiologically distinct dopamine neurons of the human brain. We found 71,022 transcribed noncoding elements, many of which were consistent with active enhancers and with regulatory mechanisms in zebrafish and mouse brains.

What can we learn about brain donors? Use of clinical information in human postmortem brain research.

Postmortem studies on the human brain reside at the core of investigations on neurologic and psychiatric disorders. Ground-breaking advances continue to be made on the pathologic basis of many of these disorders, at molecular, cellular, and neural connectivity levels. In parallel, there is increasing emphasis on improving methods to extract relevant demographic and clinical information about brain donors and, importantly, translate it into measures that can reliably and effectively be incorporated in the design and data analysis of postmortem human investigations.

Critical role of truncated α-synuclein and aggregates in Parkinson's disease and incidental Lewy body disease.

The role of Lewy bodies, Lewy neurites and α-synuclein (αSYN) in the pathophysiology and diagnosis of Parkinson's disease (PD) is unclear. We used postmortem human tissue, a panel of antibodies (Abs) and confocal microscopy to examine the three-dimensional neurochemical anatomy of the nigrostriatal system. Abs were specific to truncated (tαSYN), phosphorylated and full-length αSYN.

PGC-1α, a potential therapeutic target for early intervention in Parkinson's disease.

Parkinson's disease affects 5 million people worldwide, but the molecular mechanisms underlying its pathogenesis are still unclear. Here, we report a genome-wide meta-analysis of gene sets (groups of genes that encode the same biological pathway or process) in 410 samples from patients with symptomatic Parkinson's and subclinical disease and healthy controls. We analyzed 6.

Neuropathological heterogeneity in frontotemporal lobar degeneration with TDP-43 proteinopathy: a quantitative study of 94 cases using principal components analysis.

Studies suggest that frontotemporal lobar degeneration with transactive response DNA-binding protein of 43 kDa (TDP-43) proteinopathy (FTLD-TDP) is heterogeneous with division into four or five subtypes. To determine the degree of heterogeneity and the validity of the subtypes, we studied neuropathological variation within the frontal and temporal lobes of 94 cases of FTLD-TDP using quantitative estimates of density and principal components analysis (PCA). A PCA based on the density of TDP-43 immunoreactive neuronal cytoplasmic inclusions, oligodendroglial inclusions, neuronal intranuclear inclusions, and dystrophic neurites, surviving neurons, enlarged neurons, and vacuolation suggested that cases were not segregated into distinct subtypes.

SDF-1alpha is expressed in astrocytes and neurons in the AIDS dementia complex: an in vivo and in vitro study.

Recent in vitro studies suggest that the alpha chemokine stromal-derived factor-1alpha (SDF-1alpha) and its receptor CXCR-4 may contribute to neuronal apoptosis in HIV infection of the brain. The cellular and regional expression of this chemokine and its relationship to the AIDS dementia complex (ADC), however, have remained undetermined. Using immunohistochemistry and semiquantitative RT-PCR, we examined the expression of SDF-1alpha in the frontal cortex (FC), the adjacent deep white matter (DWM).

TorsinA protein and neuropathology in early onset generalized dystonia with GAG deletion.

Familial, early onset, generalized torsion dystonia is the most common and severe primary dystonia. Most cases are caused by a 3-bp deletion (GAG) in the coding region of the TOR1A (DYT1) gene, which is widely expressed in human brain and encodes the protein torsinA. This study compares neuropathology and torsinA expression in the normal human brain with that in dystonia cases with and without the GAG deletion.