The progression of the lesions in Alzheimer disease: insights from a prospective clinicopathological study
Senile plaques and neurofibrillary tangles are the markers of Alzheimer’s disease. They are also found in old patients who have been considered to be intellectually normal throughout their life, a situation referred to as “physiological aging”. The neurofibrillary tangles are made of abnormally phosphorylated tau. The anti-tau antibody labels not only the neurofibrillary tangles, but also the crown of the senile plaques and the neuropil threads interspersed between the cell bodies and the plaques. The senile plaque comprises a core made of Aβ peptide surrounded by a neuritic crown. The anti-Aβ antibody also labels “diffuse deposits”, i.e. ill limited areas of immunoreactivity which lacks the characteristics of the amyloid substance. The intellectual deficit appears to be statistically linked with the density of the tau-positive alterations -tangles, threads and plaque crowns — which usually appear simultaneously in a given cortical area. In the entorhinal area, their density increases proportionally to the intellectual deficit without threshold, suggesting that ageing and disease are a continuum. In the isocortex, the progression of the tau positive alterations is, on the contrary, stepwise — in a “all or none” fashion — from the hippocampus to the primary cortices, through the associative multimodal areas. The tau positive lesions probably progress through connections: they indeed disappear from areas, that have been disconnected by additional lesions (such as infarcts).
KeywordsAlzheimer Disease Entorhinal Cortex Neurofibrillary Tangle Senile Plaque Senile Dementia
Unable to display preview. Download preview PDF.
- Braak H, Duyckaerts C, Braak E, Piette F (1993) Neuropathological staging of Alzheimer-related changes correlates with psychometrically assessed intellectual status. In: Corain B, Iqbal K, Nicolini M, Winblad B, Wisniewski H, Zatta P (eds) Alzheimer’s disease: advances in clinical and basic reserch. Wiley, Chichester, pp 131–137Google Scholar
- Brion JP, Passareiro H, Nunez J, Flament-Durand J (1985) Mise en évidence immunologique de la protéine tau au niveau des lésions de dégénérescence neurofibrillaire de la maladie d’Alzheimer. Arch Biol (Brux) 95: 229–235Google Scholar
- Divry P (1927) Etude histochimique des plaques séniles. J Belge Neurol Psychist 9: 649–657Google Scholar
- Duyckaerts C, Brion J-P, Hauw J-J, Flament-Durand J (1987) Quantitative assessment of the density of neurofibrillary tangles and senile plaques in senile dementia of the Alzheimer type. Comparison of immunocytochemistry with a specific antibody and Bodian’s protargol method. Acta Neuropathol 73: 167–170PubMedCrossRefGoogle Scholar
- Duyckaerts C, Dolle MA, Seilhean D, Hauw J-J (1997) La spongiose laminaire du gyrus denté: un signe de désafférentation observé dans la maladie d’Alzheimer. De la neurophysiologie à la maladie d’Alzheimer. In: Besson JM, Bassant MH, Calvino B, Epelbaum J, Forette F, Lamour M, Pierrot-Deseilligny C, Christen Y (eds) Symposium en hommage à Yvon Lamour. Solal, Marseille, pp 173–182Google Scholar
- Hauw J-J, Uchihara T, He Y, Seilhean D, Piette F, Duyckaerts C (1997) The time course of lesions in the neocortex in ageing and Alzheimer disease. In: Iqbal K, Winblad B, Nishimura T, Takeda M, Wisniewski HM (eds) Alzheimer’s disease: biology, diagnosis and therapeutics. Wiley, ChichesterGoogle Scholar
- Masliah E, Terry RD (1993) Role of synaptic pathology in the mechanisms of denervation in Alzheimer disease. Clin Neurosci 4: 192–198Google Scholar
- Terry RD, Masliah E, Hansen LA (1994) Structural basis of the cognitive alterations in Alzheimer disease. In: Terry RD, Katzman R, Bick KL (eds) Alzheimer disease. Raven Press, New York, pp 179–196Google Scholar