Biomarkers.

Background: The amygdala is a hotspot for neuropathologies; however, it is unclear 1) which neuropathologies lead to amygdala neurodegeneration, 2) what specific amygdala subnuclei are affected, and 3) if the neuropathologies related to amygdala volume are local (inside the amygdala), or distal (in other regions). We investigate the relationships between different neuropathologies (tau, amyloid-β [Aβ], α-synuclein [α-syn], and transactive response DNA-binding protein 43 [TDP-43]) and amygdala volumes.

Method: We analyzed postmortem data from 73 individuals with and without neurodegenerative diseases (age: 77±11 [45-101] years; 26 [36%] females; 51 [70%] cognitively impaired).

Biomarkers.

Background: The medial temporal lobe (MTL) is the epicenter of both primary and concomitant molecular pathologies in Alzheimer's disease (AD). The intricate anatomy of the MTL has been the subject of extensive study over the past two centuries. However, current PET and MRI AD biomarkers use often crude parcellations of the MTL that have not been sufficiently validated vis-à-vis anatomical ground truth.

Biomarkers.

Background: Hippocampal Sclerosis of aging (HS) refers to age-related selective neuronal loss and gliosis in hippocampal cornu ammonis 1 (CA1) and subiculum that is out of proportion to tau pathology in Alzheimer's Disease (AD). HS is related to cognitive decline and memory impairments separately from other neurodegenerative pathologies. To date, in vivo imaging biomarkers of HS of aging are non-existent, and their development would greatly improve diagnosis and prognosis in memory clinics.

Developing Topics.

Background: The anterior portion of the MTL is one of the first regions targeted by pathology in sporadic Alzheimer's disease (AD) indicating the potential for imaging metrics from this region to serve as valuable imaging biomarkers. However, most existing automated approaches for MTL segmentation do not incorporate anterior MTL subregions, and the few that do fail to account for its complex anatomical variability. Leveraging a unique postmortem dataset consisting of histology and structural MRI scans we aimed to develop an anatomically valid segmentation protocol for anterior entorhinal cortex (ERC), Brodmann Area (BA) 35, and BA36 and apply it for automated MTL segmentation of in vivo 3 tesla (T) MRI.

Alzheimer's Imaging Consortium.

Background: Hippocampal Sclerosis of aging (HS) refers to age-related selective neuronal loss and gliosis in hippocampal cornu ammonis 1 (CA1) and subiculum that is out of proportion to tau pathology in Alzheimer's Disease (AD). HS is related to cognitive decline and memory impairments separately from other neurodegenerative pathologies. To date, in vivo imaging biomarkers of HS of aging are non-existent, and their development would greatly improve diagnosis and prognosis in memory clinics.

Alzheimer's Imaging Consortium.

Background: The amygdala is a hotspot for neuropathologies; however, it is unclear 1) which neuropathologies lead to amygdala neurodegeneration, 2) what specific amygdala subnuclei are affected, and 3) if the neuropathologies related to amygdala volume are local (inside the amygdala), or distal (in other regions). We investigate the relationships between different neuropathologies (tau, amyloid-ß [Aß], a-synuclein [a-syn], and transactive response DNA-binding protein 43 [TDP-43]) and amygdala volumes.

Method: We analyzed postmortem data from 73 individuals with and without neurodegenerative diseases (age: 77±11 [45-101] years; 26 [36%] females; 51 [70%] cognitively impaired).

Alzheimer's Imaging Consortium.

Background: The medial temporal lobe (MTL) is the epicenter of both primary and concomitant molecular pathologies in Alzheimer's disease (AD). The intricate anatomy of the MTL has been the subject of extensive study over the past two centuries. However, current PET and MRI AD biomarkers use often crude parcellations of the MTL that have not been sufficiently validated vis-à-vis anatomical ground truth.

, 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.

Study of the human hippocampal formation: a method for histological and magnetic resonance correlation in perinatal cases.

Little information is available on the magnetic resonance imaging (MRI) determination of the hippocampal formation (HF) during the perinatal period. However, this exploration is increasingly used, which requires defining visible HF landmarks on MRI images, validated through histological analysis. This study aims to provide a protocol to identify HF landmarks on MRI images, followed by histological validation through serial sections of the temporal lobe of the samples examined, to assess the longitudinal extent of the hippocampus during the perinatal period.

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.

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.

Neurodegenerative Diseases: A Multidisciplinary Approach.

The rapid pattern of population ageing in recent years increases the risk of appearance of associated neurodegenerative diseases. Dementias are one of the most feared disorders, and although not necessarily all elderly people have dementia, the number of people with this disease is increasing rapidly. The causes of dementia are multiple, and the diagnosis of the different types of dementia is complicated since most patients display mixed dementias and symptoms overlapping.

Neuropeptides in the developing human hippocampus under hypoxic-ischemic conditions.

The perinatal period, sensitive for newborn survival, is also one of the most critical moments in human brain development. Perinatal hypoxia due to reduced blood supply to the brain (ischemia) is one of the main causes of neonatal mortality. Brain damage caused by perinatal hypoxia-ischemia (HI) can lead to neuro- and psychological disorders.

Ultrafast determination of vitamin E using LC-ESI-MS/MS for preclinical development of new nutraceutical formulations.

Aim: We proposed a rapid and high quality method to determine α-tocopherol (α-T) in different biopharmaceutical samples using liquid chromatography-diode array detector on-line ESI-MS/MS.

Materials & Methods: A working standard solution of α-T and internal standard, phenyl-5,7-dimethyl-d6-α-tocopherol, were used for optimization and validation of the method. Levels of α-T in nanoemulsions, serum and plasma samples were evaluated.

Bioactive Flavonoids, Antioxidant Behaviour, and Cytoprotective Effects of Dried Grapefruit Peels (Citrus paradisi Macf.).

Grapefruit (Citrus paradisi Macf.) is an important cultivar of the Citrus genus which contains a number of nutrients beneficial to human health. The objective of the present study was to evaluate changes in bioactive flavonoids, antioxidant behaviour, and in vitro cytoprotective effect of processed white and pink peels after oven-drying (45°C-60°C) and freeze-drying treatments.

Prefrontal cortex afferents to the anterior temporal lobe in the Macaca fascicularis monkey.

The anatomical organization of the lateral prefrontal cortex (LPFC) afferents to the anterior part of the temporal lobe (ATL) remains to be clarified. The LPFC has two subdivisions, dorsal (dLPFC) and ventral (vLPFC), which have been linked to cognitive processes. The ATL includes several different cortical areas, namely, the temporal polar cortex and rostral parts of the perirhinal, inferotemporal, and anterior tip of the superior temporal gyrus cortices.

The mitochondria-targeted anti-oxidant MitoQ reduces aspects of mitochondrial fission in the 6-OHDA cell model of Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disorder for which available treatments provide symptom relief but do not stop disease progression. Mitochondria, and in particular mitochondrial dynamics, have been postulated as plausible pharmacological targets. Mitochondria-targeted antioxidants have been developed to prevent mitochondrial oxidative damage, and to alter the involvement of reactive oxygen species (ROS) in signaling pathways.

Convergence of olfactory and vomeronasal projections in the rat basal telencephalon.

Olfactory and vomeronasal projections have been traditionally viewed as terminating in contiguous non-overlapping areas of the basal telencephalon. Original reports, however, described areas such as the anterior medial amygdala where both chemosensory afferents appeared to overlap. We addressed this issue by injecting dextran amines in the main or accessory olfactory bulbs of rats and the results were analyzed with light and electron microscopes.

Gross anatomy dissections and self-directed learning in medicine.

The Medical School of the University of Castilla-La Mancha (UCLM, Albacete Spain) was launched in 1998 and is the most recent one in Spain. Teaching is based on small groups of students (20-25 students/group). An objective-oriented self-learning approach provides maximal autonomy and independence in the achievement of objectives by the students in close association with academic staff.

Quantitative estimation of the primary auditory cortex in human brains.

Functional neuroimaging studies in humans are common worldwide. In order to determine with more accuracy both morphometric parameters and volume of the primary auditory cortex (PAC), we studied both right and left hemispheres in human control brains. Twelve hemispheres were systematically sectioned orthogonal to the anterior-posterior commissures (ac-pc line).