title: Hierarchical Distribution of the Tau Cytoskeletal Pathology in the Thalamus of Alzheimer's Disease Patients.
abstract: In spite of considerable progress in neuropathological research on Alzheimer's disease (AD), knowledge regarding the exact pathoanatomical distribution of the tau cytoskeletal pathology in the thalamus of AD patients in the advanced Braak and Braak AD stages V or VI of the cortical cytoskeletal pathology is still fragmentary. Investigation of serial 100 μm-thick brain tissue sections through the thalamus of clinically diagnosed AD patients with Braak and Braak AD stage V or VI cytoskeletal pathologies immunostained with the anti-tau AT8 antibody, along with the affection of the extraterritorial reticular nucleus of the thalamus, reveals a consistent and severe tau immunoreactive cytoskeletal pathology in the limbic nuclei of the thalamus (e.g., paraventricular, anterodorsal and laterodorsal nuclei, limitans-suprageniculate complex). The thalamic nuclei integrated into the associative networks of the human brain (e.g., ventral anterior and mediodorsal nuclei) are only mildly affected, while its motor precerebellar (ventral lateral nucleus) and sensory nuclei (e.g., lateral and medial geniculate bodies, ventral posterior medial and lateral nuclei, parvocellular part of the ventral posterior medial nucleus) are more or less spared. The highly stereotypical and characteristic thalamic distribution pattern of the AD-related tau cytoskeletal pathology represents an anatomical mirror of the hierarchical topographic distribution of the cytoskeletal pathology in the interconnected regions of the cerebral cortex of AD patients. These pathoanatomical parallels support the pathophysiological concept of a transneuronal spread of the disease process of AD along anatomical pathways. The AD-related tau cytoskeletal pathology in the thalamus most likely contributes substantially to the neuropsychiatric disease symptoms (e.g., dementia), attention deficits, oculomotor dysfunctions, altered non-discriminative aspects of pain experience of AD patients, and the disruption of their waking and sleeping patterns.
authors.affiliation: Dr. Senckenbergisches Chronomedizinisches Institut, Goethe-University, Frankfurt/Main, Germany.
authors.forename: Udo
authors.initials: U
authors.lastname: Rüb
authors.affiliation: Dr. Senckenbergisches Chronomedizinisches Institut, Goethe-University, Frankfurt/Main, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Stratmann
authors.affiliation: Morphological Brain Research Unit, Psychiatric Clinic, Julius Maximilians University, Würzburg, Germany.
authors.forename: Helmut
authors.initials: H
authors.lastname: Heinsen
authors.affiliation: Institute of Clinical Neuroanatomy, Neuroscience Center, Goethe-University, Frankfurt/Main, Germany.
authors.forename: Domenico
authors.initials: D
authors.lastname: Del Turco
authors.affiliation: Institute of Clinical Neuroanatomy, Neuroscience Center, Goethe-University, Frankfurt/Main, Germany.
authors.forename: Estifanos
authors.initials: E
authors.lastname: Ghebremedhin
authors.affiliation: Dr. Senckenbergisches Chronomedizinisches Institut, Goethe-University, Frankfurt/Main, Germany.
authors.forename: Kay
authors.initials: K
authors.lastname: Seidel
authors.affiliation: Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Wilfred
authors.initials: W
authors.lastname: den Dunnen
authors.affiliation: Dr. Senckenbergisches Chronomedizinisches Institut, Goethe-University, Frankfurt/Main, Germany.
authors.forename: Horst-Werner
authors.initials: HW
authors.lastname: Korf
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology*; D003599:Cytoskeleton / Q000378:metabolism*; D006801:Humans; D013788:Thalamus / Q000378:metabolism* / Q000473:pathology*; D016875:tau Proteins / Q000378:metabolism*
chemical_list: C054369:MAPT protein, human; D016875:tau Proteins
keywords: Alzheimer’s disease; cytoskeletal pathology; pathoanatomy; tau; thalamus