Probing the correlation of neuronal loss, neurofibrillary tangles, and cell death markers across the Alzheimer's disease Braak stages: a quantitative study in humans.

Clarifying the mechanisms connecting neurofibrillary tangle (NFT) neurotoxicity to neuronal dysfunction in humans is likely to be pivotal for developing effective treatments for Alzheimer's disease (AD). To model the temporal progression of AD in humans, we used a collection of brains with controls and individuals from each Braak stage to quantitatively investigate the correlation between intraneuronal caspase activation or macroautophagy markers, NFT burden, and neuronal loss, in the dorsal raphe nucleus and locus coeruleus, the earliest vulnerable areas to NFT accumulation. We fit linear regressions with each count as outcomes, with Braak score and age as the predictors.

Locus coeruleus volume and cell population changes during Alzheimer's disease progression: A stereological study in human postmortem brains with potential implication for early-stage biomarker discovery.

Introduction: Alzheimer's disease (AD) progression follows a specific spreading pattern, emphasizing the need to characterize those brain areas that degenerate first. The brainstem's locus coeruleus (LC) is the first area to develop neurofibrillary changes (neurofibrillary tangles [NFTs]).

Methods: The methods include unbiased stereological analyses in human brainstems to estimate LC volume and neuronal population in controls and individuals across all AD stages.

Brainstem: neglected locus in neurodegenerative diseases.

The most frequent neurodegenerative diseases (NDs) are Alzheimer's disease (AD), Parkinson's disease (PD), and frontotemporal lobar degeneration associated with protein TDP-43 (FTLD-TDP). Neuropathologically, NDs are characterized by abnormal intracellular and extra-cellular protein deposits and by disease-specific neuronal death. Practically all terminal stages of NDs are clinically associated with dementia.

Gene expression of neuregulin-1 isoforms in different brain regions of elderly schizophrenia patients.

One important risk gene in schizophrenia is neuregulin-1 (NRG1), which is expressed in different isoforms in the brain. To determine if alterations of NRG1 are present in schizophrenia, we measured gene expression of NRG1 and its main isoforms as well as the impact of genetic variation of NRG1 in an exploratory study examining three brain regions instead of only one as published so far. In all, we examined post-mortem samples from 11 schizophrenia patients and eight normal subjects.

Brainstem pathology and non-motor symptoms in PD.

Parkinson's disease (PD) is considered a multisystem disorder involving dopaminergic, noradrenergic, serotoninergic, and cholinergic systems, characterized by motor and non-motor symptoms. The causes of the non-motor symptoms in PD are multifactorial and unlikely to be explained by single lesions. However, several evidence link them to damage of specific brainstem nuclei.