Contribution of mixed pathology to medial temporal lobe atrophy in Alzheimer's disease. 2020

Robin de Flores, and Laura E M Wisse, and Sandhitsu R Das, and Long Xie, and Corey T McMillan, and John Q Trojanowski, and John L Robinson, and Murray Grossman, and Edward Lee, and David J Irwin, and Paul A Yushkevich, and David A Wolk
Department of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

It is unclear how different proteinopathies (tau, transactive response DNA-binding protein 43 [TDP-43], amyloid β [Aβ], and α-synuclein) contribute to atrophy within medial temporal lobe (MTL) subregions in Alzheimer's disease (AD). We utilized antemortem structural magnetic resonance imaging (MRI) data to measure MTL substructures and examined the relative contribution of tau, TDP-43, Aβ, and α-synuclein measured in post-mortem tissue from 92 individuals with intermediate to high AD neuropathology. Receiver-operating characteristic (ROC) curves were analyzed for each subregion in order to discriminate TDP-43-negative and TDP-43-positive patients. TDP-43 was strongly associated with anterior MTL regions, whereas tau was relatively more associated with the posterior hippocampus. Among the MTL regions, the anterior hippocampus showed the highest area under the ROC curve (AUC). We found specific contributions of different pathologies on MTL substructure in this population with AD neuropathology. The anterior hippocampus may be a relevant region to detect concomitant TDP-43 pathology in the MTL of patients with AD.

UI MeSH Term Description Entries
D008279 Magnetic Resonance Imaging Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. Chemical Shift Imaging,MR Tomography,MRI Scans,MRI, Functional,Magnetic Resonance Image,Magnetic Resonance Imaging, Functional,Magnetization Transfer Contrast Imaging,NMR Imaging,NMR Tomography,Tomography, NMR,Tomography, Proton Spin,fMRI,Functional Magnetic Resonance Imaging,Imaging, Chemical Shift,Proton Spin Tomography,Spin Echo Imaging,Steady-State Free Precession MRI,Tomography, MR,Zeugmatography,Chemical Shift Imagings,Echo Imaging, Spin,Echo Imagings, Spin,Functional MRI,Functional MRIs,Image, Magnetic Resonance,Imaging, Magnetic Resonance,Imaging, NMR,Imaging, Spin Echo,Imagings, Chemical Shift,Imagings, Spin Echo,MRI Scan,MRIs, Functional,Magnetic Resonance Images,Resonance Image, Magnetic,Scan, MRI,Scans, MRI,Shift Imaging, Chemical,Shift Imagings, Chemical,Spin Echo Imagings,Steady State Free Precession MRI
D004268 DNA-Binding Proteins Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases. DNA Helix Destabilizing Proteins,DNA-Binding Protein,Single-Stranded DNA Binding Proteins,DNA Binding Protein,DNA Single-Stranded Binding Protein,SS DNA BP,Single-Stranded DNA-Binding Protein,Binding Protein, DNA,DNA Binding Proteins,DNA Single Stranded Binding Protein,DNA-Binding Protein, Single-Stranded,Protein, DNA-Binding,Single Stranded DNA Binding Protein,Single Stranded DNA Binding Proteins
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000544 Alzheimer Disease A degenerative disease of the BRAIN characterized by the insidious onset of DEMENTIA. Impairment of MEMORY, judgment, attention span, and problem solving skills are followed by severe APRAXIAS and a global loss of cognitive abilities. The condition primarily occurs after age 60, and is marked pathologically by severe cortical atrophy and the triad of SENILE PLAQUES; NEUROFIBRILLARY TANGLES; and NEUROPIL THREADS. (From Adams et al., Principles of Neurology, 6th ed, pp1049-57) Acute Confusional Senile Dementia,Alzheimer's Diseases,Dementia, Alzheimer Type,Dementia, Senile,Presenile Alzheimer Dementia,Senile Dementia, Alzheimer Type,Alzheimer Dementia,Alzheimer Disease, Early Onset,Alzheimer Disease, Late Onset,Alzheimer Sclerosis,Alzheimer Syndrome,Alzheimer Type Senile Dementia,Alzheimer's Disease,Alzheimer's Disease, Focal Onset,Alzheimer-Type Dementia (ATD),Dementia, Presenile,Dementia, Primary Senile Degenerative,Early Onset Alzheimer Disease,Familial Alzheimer Disease (FAD),Focal Onset Alzheimer's Disease,Late Onset Alzheimer Disease,Primary Senile Degenerative Dementia,Senile Dementia, Acute Confusional,Alzheimer Dementias,Alzheimer Disease, Familial (FAD),Alzheimer Diseases,Alzheimer Type Dementia,Alzheimer Type Dementia (ATD),Alzheimers Diseases,Dementia, Alzheimer,Dementia, Alzheimer-Type (ATD),Familial Alzheimer Diseases (FAD),Presenile Dementia,Sclerosis, Alzheimer,Senile Dementia
D001284 Atrophy Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. Atrophies
D013702 Temporal Lobe Lower lateral part of the cerebral hemisphere responsible for auditory, olfactory, and semantic processing. It is located inferior to the lateral fissure and anterior to the OCCIPITAL LOBE. Anterior Temporal Lobe,Brodmann Area 20,Brodmann Area 21,Brodmann Area 22,Brodmann Area 37,Brodmann Area 38,Brodmann Area 52,Brodmann's Area 20,Brodmann's Area 21,Brodmann's Area 22,Brodmann's Area 37,Brodmann's Area 38,Brodmann's Area 52,Inferior Temporal Gyrus,Middle Temporal Gyrus,Parainsular Area,Fusiform Gyrus,Gyrus Fusiformis,Gyrus Temporalis Superior,Inferior Horn of Lateral Ventricle,Inferior Horn of the Lateral Ventricle,Lateral Occipito-Temporal Gyrus,Lateral Occipitotemporal Gyrus,Occipitotemporal Gyrus,Planum Polare,Superior Temporal Gyrus,Temporal Cortex,Temporal Gyrus,Temporal Horn,Temporal Horn of the Lateral Ventricle,Temporal Operculum,Temporal Region,Temporal Sulcus,Anterior Temporal Lobes,Area 20, Brodmann,Area 20, Brodmann's,Area 21, Brodmann,Area 21, Brodmann's,Area 22, Brodmann,Area 22, Brodmann's,Area 37, Brodmann,Area 37, Brodmann's,Area 38, Brodmann,Area 38, Brodmann's,Area 52, Brodmann,Area 52, Brodmann's,Area, Parainsular,Areas, Parainsular,Brodmanns Area 20,Brodmanns Area 21,Brodmanns Area 22,Brodmanns Area 37,Brodmanns Area 38,Brodmanns Area 52,Cortex, Temporal,Gyrus, Fusiform,Gyrus, Inferior Temporal,Gyrus, Lateral Occipito-Temporal,Gyrus, Lateral Occipitotemporal,Gyrus, Middle Temporal,Gyrus, Occipitotemporal,Gyrus, Superior Temporal,Gyrus, Temporal,Horn, Temporal,Lateral Occipito Temporal Gyrus,Lobe, Anterior Temporal,Lobe, Temporal,Occipito-Temporal Gyrus, Lateral,Occipitotemporal Gyrus, Lateral,Operculum, Temporal,Parainsular Areas,Region, Temporal,Sulcus, Temporal,Temporal Cortices,Temporal Gyrus, Inferior,Temporal Gyrus, Middle,Temporal Gyrus, Superior,Temporal Horns,Temporal Lobe, Anterior,Temporal Lobes,Temporal Lobes, Anterior,Temporal Regions
D016229 Amyloid beta-Peptides Peptides generated from AMYLOID BETA-PEPTIDES PRECURSOR. An amyloid fibrillar form of these peptides is the major component of amyloid plaques found in individuals with Alzheimer's disease and in aged individuals with trisomy 21 (DOWN SYNDROME). The peptide is found predominantly in the nervous system, but there have been reports of its presence in non-neural tissue. Alzheimer beta-Protein,Amyloid Protein A4,Amyloid beta-Peptide,Amyloid beta-Protein,beta Amyloid,beta-Amyloid Protein,Alzheimer's ABP,Alzheimer's Amyloid Fibril Protein,Amyloid AD-AP,Amyloid Fibril Protein, Alzheimer's,Amyloid beta-Proteins,ABP, Alzheimer's,AD-AP, Amyloid,Alzheimer ABP,Alzheimer beta Protein,Alzheimers ABP,Amyloid AD AP,Amyloid beta Peptide,Amyloid beta Peptides,Amyloid beta Protein,Amyloid beta Proteins,Amyloid, beta,Protein A4, Amyloid,Protein, beta-Amyloid,beta Amyloid Protein,beta-Peptide, Amyloid,beta-Peptides, Amyloid,beta-Protein, Alzheimer,beta-Protein, Amyloid,beta-Proteins, Amyloid
D016875 tau Proteins Microtubule-associated proteins that are mainly expressed in neurons. Tau proteins constitute several isoforms and play an important role in the assembly of tubulin monomers into microtubules and in maintaining the cytoskeleton and axonal transport. Aggregation of specific sets of tau proteins in filamentous inclusions is the common feature of intraneuronal and glial fibrillar lesions (NEUROFIBRILLARY TANGLES; NEUROPIL THREADS) in numerous neurodegenerative disorders (ALZHEIMER DISEASE; TAUOPATHIES). tau Protein,Protein, tau,Proteins, tau
D051844 alpha-Synuclein A synuclein that is a major component of LEWY BODIES and plays a role in SYNUCLEINOPATHIES, neurodegeneration and neuroprotection. Non-AB Component of AD Amyloid Protein,Non AB Component of AD Amyloid Protein,alpha Synuclein

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