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Alzheimer-related tau-pathology in the perforant path target zone and in the hippocampal stratum oriens and radiatum correlates with onset and degree of dementia.
Exp Neurol. 2000 May; 163(1):98-110.EN

Abstract

Abnormal phosphorylation of the tau-protein is regarded as a crucial step in the formation of neurofibrillary tangles in the neuronal cell body and neuropil threads in dendrites. We studied the effects of tau-pathology on the clinical expression of dementia in 106 autopsy cases in the entorhinal region, the hippocampal stratum oriens, the stratum radiatum, and the perforant path target zone. The first cytoskeletal lesions were located in the perikarya and dendrites of the pre-alpha cells of the transentorhinal and entorhinal region. Next, abnormally phosphorylated tau-protein (PHF-tau) was found in the neuropil of the CA1-subiculum region. Thereafter, the stratum radiatum and stratum oriens began to be involved in PHF-tau pathology in Braak stage II. In the Braak stages IV and V, the stratum radiatum was completely involved, the stratum oriens increasingly so. Beginning in Braak stage III, we noted cases having PHF-tau pathology in the perforant path target zone of the outer molecular layer of the dentate gyrus. The increase of this pathology with ever greater involvement on the part of the entorhinohippocampal circuit correlated significantly not only with the Braak stages and with the neurochemically determined hippocampal content of PHF-tau but also with the degree of dementia as defined by the clinical dementia rating (CDR) scale. The affection of the stratum oriens in combination with PHF-tau pathology in the stratum radiatum and in the outer molecular layer of the dentate gyrus was encountered almost exclusively in demented individuals (CDR 1-3). These results indicate that axonal PHF-tau pathology in hippocampal pathways presumably is critical for the clinical expression of dementia and may constitute an anatomical substrate of clinically verifiable memory dysfunction in Alzheimer's disease.

Authors+Show Affiliations

Department of Neuropathology, University of Leipzig, Leipzig, D-04103, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

10785448

Citation

Thal, D R., et al. "Alzheimer-related Tau-pathology in the Perforant Path Target Zone and in the Hippocampal Stratum Oriens and Radiatum Correlates With Onset and Degree of Dementia." Experimental Neurology, vol. 163, no. 1, 2000, pp. 98-110.
Thal DR, Holzer M, Rüb U, et al. Alzheimer-related tau-pathology in the perforant path target zone and in the hippocampal stratum oriens and radiatum correlates with onset and degree of dementia. Exp Neurol. 2000;163(1):98-110.
Thal, D. R., Holzer, M., Rüb, U., Waldmann, G., Günzel, S., Zedlick, D., & Schober, R. (2000). Alzheimer-related tau-pathology in the perforant path target zone and in the hippocampal stratum oriens and radiatum correlates with onset and degree of dementia. Experimental Neurology, 163(1), 98-110.
Thal DR, et al. Alzheimer-related Tau-pathology in the Perforant Path Target Zone and in the Hippocampal Stratum Oriens and Radiatum Correlates With Onset and Degree of Dementia. Exp Neurol. 2000;163(1):98-110. PubMed PMID: 10785448.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Alzheimer-related tau-pathology in the perforant path target zone and in the hippocampal stratum oriens and radiatum correlates with onset and degree of dementia. AU - Thal,D R, AU - Holzer,M, AU - Rüb,U, AU - Waldmann,G, AU - Günzel,S, AU - Zedlick,D, AU - Schober,R, PY - 2000/4/29/pubmed PY - 2000/6/17/medline PY - 2000/4/29/entrez SP - 98 EP - 110 JF - Experimental neurology JO - Exp Neurol VL - 163 IS - 1 N2 - Abnormal phosphorylation of the tau-protein is regarded as a crucial step in the formation of neurofibrillary tangles in the neuronal cell body and neuropil threads in dendrites. We studied the effects of tau-pathology on the clinical expression of dementia in 106 autopsy cases in the entorhinal region, the hippocampal stratum oriens, the stratum radiatum, and the perforant path target zone. The first cytoskeletal lesions were located in the perikarya and dendrites of the pre-alpha cells of the transentorhinal and entorhinal region. Next, abnormally phosphorylated tau-protein (PHF-tau) was found in the neuropil of the CA1-subiculum region. Thereafter, the stratum radiatum and stratum oriens began to be involved in PHF-tau pathology in Braak stage II. In the Braak stages IV and V, the stratum radiatum was completely involved, the stratum oriens increasingly so. Beginning in Braak stage III, we noted cases having PHF-tau pathology in the perforant path target zone of the outer molecular layer of the dentate gyrus. The increase of this pathology with ever greater involvement on the part of the entorhinohippocampal circuit correlated significantly not only with the Braak stages and with the neurochemically determined hippocampal content of PHF-tau but also with the degree of dementia as defined by the clinical dementia rating (CDR) scale. The affection of the stratum oriens in combination with PHF-tau pathology in the stratum radiatum and in the outer molecular layer of the dentate gyrus was encountered almost exclusively in demented individuals (CDR 1-3). These results indicate that axonal PHF-tau pathology in hippocampal pathways presumably is critical for the clinical expression of dementia and may constitute an anatomical substrate of clinically verifiable memory dysfunction in Alzheimer's disease. SN - 0014-4886 UR - https://www.unboundmedicine.com/medline/citation/10785448/Alzheimer_related_tau_pathology_in_the_perforant_path_target_zone_and_in_the_hippocampal_stratum_oriens_and_radiatum_correlates_with_onset_and_degree_of_dementia_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-4886(00)97380-1 DB - PRIME DP - Unbound Medicine ER -