Cortical mapping of Alzheimer pathology in brains of aged non-demented subjects

1. The presence of Alzheimer-type neurofibrillary pathology and amyloid deposits within the brains of 27 aged non-demented subjects was investigated by immunoblotting and immunohistochemistry using antibodies directed against pathological Tau proteins 55, 64 and 69 and beta A4 respectively. 2. The abnormal Tau triplet, a biochemical marker of neurofibrillary degeneration was quantified by western blot and densitometric analysis in several cortical areas including the entorhinal cortex (EC), hippocampus and Brodmann areas (BA) 38, 20, 22, 35, 9, 44 and 39. 3. The abnormal Tau triplet was detected in the EC and the hippocampus of most of the controls aged over 70 years. In few control cases abnormal Tau proteins were also detected in the isocortex, in BA38 alone or also in BA20. Some cases and especially those with Tau pathology in the temporal lobe contained numerous senile plaques (SP) in the neocortex. 4. The authors conclude that control cases with Tau pathology in the temporal lobe and numerous SP in the neocortex were likely to be subclinical stages of AD whereas others with Tau pathology exclusively detected in the EC and hippocampus and without or few SP in the neocortex were related to normal aging.

[1]  J. Price The relationship between tangle and plaque formation during healthy aging and mild dementia , 1993, Neurobiology of Aging.

[2]  S. M. Sumi,et al.  The Consortium to Establish a Registry for Alzheimer's Disease (CERAD) , 1991, Neurology.

[3]  N. Cairns,et al.  Tau in Alzheimer's disease and Down's syndrome is insoluble and abnormally phosphorylated. , 1991, The Biochemical journal.

[4]  M. Folstein,et al.  Clinical diagnosis of Alzheimer's disease , 1984, Neurology.

[5]  H. Braak,et al.  Occurrence of neuropil threads in the senile human brain and in Alzheimer's disease: A third location of paired helical filaments outside of neurofibrillary tangles and neuritic plaques , 1986, Neuroscience Letters.

[6]  P. Yates,et al.  THE TOPOGRAPHIC DISTRIBUTION OF SENILE PLAQUES AND NEUROFIBRILLARY TANGLES IN THE BRAINS OF NON‐DEMENTED PERSONS OF DIFFERENT AGES , 1987, Neuropathology and applied neurobiology.

[7]  Peter Davies,et al.  Identification of normal and pathological aging in prospectively studied nondemented elderly humans , 1992, Neurobiology of Aging.

[8]  A. Delacourte,et al.  Presence of abnormally phosphorylated Tau proteins in the entorhinal cortex of aged non-demented subjects , 1992, Neuroscience Letters.

[9]  S. Folstein,et al.  "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. , 1975, Journal of psychiatric research.

[10]  P. Hof,et al.  Neurofibrillary degeneration in amyotrophic lateral sclerosis/parkinsonism-dementia complex of Guam. Immunochemical characterization of tau proteins. , 1995, The American journal of pathology.

[11]  M. Roth,et al.  Regional Distribution of Paired Helical Filaments and Normal Tau Proteins in Aging and in Alzheimer's Disease with and without Occipital Lobe Involvement , 1992 .

[12]  J. Morrison,et al.  Neurofibrillary tangle densities in the hippocampal formation in a non-demented population define subgroups of patients with differential early pathologic changes , 1993, Neuroscience Letters.

[13]  J. Price,et al.  The distribution of tangles, plaques and related immunohistochemical markers in healthy aging and Alzheimer's disease , 1991, Neurobiology of Aging.

[14]  J. Price,et al.  Very mild Alzheimer's disease , 1991, Neurology.

[15]  Bradley T. Hyman,et al.  Neurofibrillary tangles but not senile plaques parallel duration and severity of Alzheimer's disease , 1992, Neurology.

[16]  Jan Voogd,et al.  The human central nervous system : a synopsis and atlas , 1978 .

[17]  J. Trojanowski,et al.  Regions with abundant neurofibrillary pathology in human brain exhibit a selective reduction in levels of binding-competent tau and accumulation of abnormal tau-isoforms (A68 proteins). , 1992, Laboratory investigation; a journal of technical methods and pathology.

[18]  Z. Khachaturian Diagnosis of Alzheimer's disease. , 1985, Archives of neurology.

[19]  U. K. Laemmli,et al.  Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4 , 1970, Nature.

[20]  G. Glenner,et al.  Alzheimer's disease: Initial report of the purification and characterization of a novel cerebrovascular amyloid protein , 1984 .

[21]  J. Miller,et al.  Neuropathological indexes of Alzheimer's disease in demented and nondemented persons aged 80 years and older. , 1993, Archives of neurology.

[22]  J. Trojanowski,et al.  Intraneuronal and extracellular neurofibrillary tangles exhibit mutually exclusive cytoskeletal antigens , 1988, Annals of neurology.

[23]  S. Mirra,et al.  Making the diagnosis of Alzheimer's disease. A primer for practicing pathologists. , 1993, Archives of pathology & laboratory medicine.

[24]  J. Morrison,et al.  Evidence for early vulnerability of the medial and inferior aspects of the temporal lobe in an 82-year-old patient with preclinical signs of dementia. Regional and laminar distribution of neurofibrillary tangles and senile plaques. , 1992, Archives of neurology.

[25]  J. M. Anderson,et al.  A quantitative histological study of early clinical and preclinical Alzheimer's disease , 1990, Neuropathology and applied neurobiology.

[26]  A. Delacourte,et al.  Characterization of two pathological Tau protein variants in Alzheimer brain cortices , 1989, Journal of the Neurological Sciences.

[27]  K. Brodmann Vergleichende Lokalisationslehre der Großhirnrinde : in ihren Prinzipien dargestellt auf Grund des Zellenbaues , 1985 .

[28]  M. Kidd Paired Helical Filaments in Electron Microscopy of Alzheimer's Disease , 1963, Nature.

[29]  J. Trojanowski,et al.  A68: a major subunit of paired helical filaments and derivatized forms of normal Tau. , 1991, Science.

[30]  J. Price,et al.  Retrospective postmortem dementia assessment. Validation of a new clinical interview to assist neuropathologic study. , 1991, Archives of neurology.