, perfusion protocol for human brain fixation compatible with microscopy, MRI techniques, and anatomical studies.

We present a method for human brain fixation based on simultaneous perfusion of 4% paraformaldehyde through carotids after a flush with saline. The left carotid cannula is used to perfuse the body with 10% formalin, to allow further use of the body for anatomical research or teaching. The aim of our method is to develop a vascular fixation protocol for the human brain, by adapting protocols that are commonly used in experimental animal studies.

Associations of phosphorylated tau pathology with whole-hemisphere ex vivo morphometry in 7 tesla MRI.

Introduction: Neurodegenerative disorders are associated with different pathologies that often co-occur but cannot be measured specifically with in vivo methods.

Methods: Thirty-three brain hemispheres from donors with an Alzheimer's disease (AD) spectrum diagnosis underwent T2-weighted magnetic resonance imaging (MRI). Gray matter thickness was paired with histopathology from the closest anatomic region in the contralateral hemisphere.

Ex vivo MRI atlas of the human medial temporal lobe: characterizing neurodegeneration due to tau pathology.

Tau neurofibrillary tangle (NFT) pathology in the medial temporal lobe (MTL) is closely linked to neurodegeneration, and is the early pathological change associated with Alzheimer's disease (AD). To elucidate patterns of structural change in the MTL specifically associated with tau pathology, we compared high-resolution ex vivo MRI scans of human postmortem MTL specimens with histology-based pathological assessments of the MTL. MTL specimens were obtained from twenty-nine brain donors, including patients with AD, other dementias, and individuals with no known history of neurological disease.

Glioblastoma Proximity to the Lateral Ventricle Alters Neurogenic Cell Populations of the Subventricular Zone.

Despite current strategies combining surgery, radiation, and chemotherapy, glioblastoma (GBM) is the most common and aggressive malignant primary brain tumor in adults. Tumor location plays a key role in the prognosis of patients, with GBM tumors located in close proximity to the lateral ventricles (LVs) resulting in worse survival expectancy and higher incidence of distal recurrence. Though the reason for worse prognosis in these patients remains unknown, it may be due to proximity to the subventricular zone (SVZ) neurogenic niche contained within the lateral wall of the LVs.

Three-dimensional mapping of neurofibrillary tangle burden in the human medial temporal lobe.

Tau protein neurofibrillary tangles are closely linked to neuronal/synaptic loss and cognitive decline in Alzheimer's disease and related dementias. Our knowledge of the pattern of neurofibrillary tangle progression in the human brain, critical to the development of imaging biomarkers and interpretation of in vivo imaging studies in Alzheimer's disease, is based on conventional two-dimensional histology studies that only sample the brain sparsely. To address this limitation, ex vivo MRI and dense serial histological imaging in 18 human medial temporal lobe specimens (age 75.

Neuronal volume of the hippocampal regions in ageing.

The hippocampal formation (HF) has an important role in different human capacities, such as memory processing and emotional expression. Both extensive changes and limited variations of its components can cause clinically expressed dysfunctions. Although there remains no effective treatment for diseases caused by pathological changes in this brain region, detection of these changes, even minimally, could allow us to develop early interventions and establish corrective measures.

Neurogenesis, Neurodegeneration, Interneuron Vulnerability, and Amyloid-β in the Olfactory Bulb of APP/PS1 Mouse Model of Alzheimer's Disease.

Alzheimer's disease (AD) is the most prevalent neurodegenerative disease, mostly idiopathic and with palliative treatment. Neuropathologically, it is characterized by intracellular neurofibrillary tangles of tau protein and extracellular plaques of amyloid β peptides. The relationship between AD and neurogenesis is unknown, but two facts are particularly relevant.

Hippocampal α-synuclein and interneurons in Parkinson's disease: Data from human and mouse models.

Background: Dementia is a nonmotor feature of Parkinson's disease, arising around the onset of hippocampal pathology in stage IV of the disease, from where it progress to the isocortex. Differential α-synuclein involvement in hippocampal interneuron populations remains unknown. The objective of this study was to analyze the involvement of α-synuclein in hippocampal interneurons in an α-synucleinopathy mouse model and in the brains of Parkinson's disease patients.

Interneurons in the human olfactory system in Alzheimer's disease.

The principal olfactory structures display Alzheimer's disease (AD) related pathology at early stages of the disease. Consequently, olfactory deficits are among the earliest symptoms. Reliable olfactory tests for accurate clinical diagnosis are rarely made.

Olfactory and cortical projections to bulbar and hippocampal adult-born neurons.

New neurons are continually generated in the subependymal layer of the lateral ventricles and the subgranular zone of dentate gyrus during adulthood. In the subventricular zone, neuroblasts migrate a long distance to the olfactory bulb where they differentiate into granule or periglomerular interneurons. In the hippocampus, neuroblasts migrate a short distance from the subgranular zone to the granule cell layer of the dentate gyrus to become granule neurons.

α-Synuclein staging in the amygdala of a Parkinson's disease model: cell types involved.

Lewy bodies (ubiquitin and α-synuclein aggregates) can be detected in brain areas in a predictable sequence of six neuropathological stages in Parkinson's disease. Brainstem and olfactory structures are involved in stage 1, whereas the substantia nigra and amygdala are involved in stage 3, prior to cortical spreading. Amygdaloid pathology has been suggested to contribute to non-motor symptoms such as olfactory dysfunction and emotional impairment.

Interneurons, tau and amyloid-β in the piriform cortex in Alzheimer's disease.

Impaired olfaction has been described as an early symptom of Alzheimer's disease. Neuroanatomical changes underlying this deficit in the olfactory system are largely unknown. Interestingly, neuropathology begins in the transentorhinal cortex and extends to the neighboring limbic system and basal telencephalic structures that mediate olfactory processing, including the anterior olfactory nucleus and olfactory bulb.

α-Synuclein in the olfactory system in Parkinson's disease: role of neural connections on spreading pathology.

Parkinson's disease (PD) is a neurodegenerative disease characterized by bradykinesia, rigidity, resting tremor, and postural instability. Neuropathologically, intracellular aggregates of α-synuclein in Lewy bodies and Lewy neurites appear in particular brain areas according to a sequence of stages. Clinical diagnosis is usually established when motor symptoms are evident (corresponding to Braak stage III or later), years or even decades after onset of the disease.

Interneurons and beta-amyloid in the olfactory bulb, anterior olfactory nucleus and olfactory tubercle in APPxPS1 transgenic mice model of Alzheimer's disease.

Impaired olfaction has been described as an early symptom in Alzheimer's disease (AD). Neuroanatomical changes underlying this deficit in the olfactory system are largely unknown. Given that interneuron populations are crucial in olfactory information processing, we have quantitatively analyzed somatostatin- (SOM), parvalbumin- (PV), and calretinin-expressing (CR) cells in the olfactory bulb, anterior olfactory nucleus, and olfactory tubercle in PS1 x APP double transgenic mice model of AD.

Centrifugal telencephalic afferent connections to the main and accessory olfactory bulbs.

Parallel to the olfactory system, most mammals possess an accessory olfactory or vomeronasal system. The olfactory and vomeronasal epithelia project to the main and accessory olfactory bulbs, which in turn project to adjacent areas of the telencephalon, respectively. New data indicate that projections arising from the main and accessory olfactory bulbs partially converge in the rostral telencephalon and are non-overlapping at caudal telencephalic levels.

Differential expression of interneuron populations and correlation with amyloid-β deposition in the olfactory cortex of an AβPP/PS1 transgenic mouse model of Alzheimer's disease.

Impaired olfaction is an early symptom of Alzheimer's disease (AD). Neuroanatomical changes underlying this deficit in the olfactory system are largely unknown. Cell neurodegeneration is known to involve, among others, somatostatin (SST)- and calcium-binding protein-positive cells.

α-Synuclein in the olfactory system of a mouse model of Parkinson's disease: correlation with olfactory projections.

Olfactory deficits are an early feature of Parkinson's disease (PD). Neuropathologically, α-synucleinopathy (Lewy bodies and neurites) is observed earlier (stage 1) in the olfactory system than in the substantia nigra (stage 3), and this could underlies the early olfactory symptoms. In the present report, we analyzed the distribution of α-synuclein deposits in tertiary olfactory structures (anterior olfactory nucleus, olfactory tubercle, piriform cortex, posterolateral cortical amygdala and lateral entorhinal cortex) of homozygous transgenic mice (aged 2-8 months) overexpressing the human A53T variant of α-synuclein.

Maturation of newly born vomeronasal neurons in the adult mice.

The olfactory and vomeronasal epithelia detect chemical stimuli in most tetrapods. Both epithelia undergo neural replacement during adulthood. In the central regions of vomeronasal epithelium, similar rates of neurogenesis and apoptosis evidence balanced replacement mechanisms.

Staging of alpha-synuclein in the olfactory bulb in a model of Parkinson's disease: cell types involved.

Impaired olfaction is an early symptom of Parkinson's disease. The underlying neuropathology likely includes alpha-synucleinopathy in the olfactory bulb at an earlier stage (Braak's stage1) than pathology in the substantia nigra, which is not observed until stage 3. In this report, we investigated the distribution and cell types affected by alpha-synuclein in the olfactory bulb of transgenic mice (2-8 months of age) expressing the human A53T variant of alpha-synuclein.