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Classification and basic pathology of Alzheimer disease

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Abstract

The lesions of Alzheimer disease include accumulation of proteins, losses of neurons and synapses, and alterations related to reactive processes. Extracellular Aβ accumulation occurs in the parenchyma as diffuse, focal or stellate deposits. It may involve the vessel walls of arteries, veins and capillaries. The cases in which the capillary vessel walls are affected have a higher probability of having one or two apoε 4 alleles. Parenchymal as well as vascular Aβ deposition follows a stepwise progression. Tau accumulation, probably the best histopathological correlate of the clinical symptoms, takes three aspects: in the cell body of the neuron as neurofibrillary tangle, in the dendrites as neuropil threads, and in the axons forming the senile plaque neuritic corona. The progression of tau pathology is stepwise and stereotyped from the entorhinal cortex, through the hippocampus, to the isocortex. The neuronal loss is heterogeneous and area-specific. Its mechanism is still discussed. The timing of the synaptic loss, probably linked to Aβ peptide itself, maybe as oligomers, is also controversial. Various clinico-pathological types of Alzheimer disease have been described, according to the type of the lesions (plaque only and tangle predominant), the type of onset (focal onset), the cause (genetic or sporadic) and the associated lesions (Lewy bodies, vascular lesions, hippocampal sclerosis, TDP-43 inclusions and argyrophilic grain disease).

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Acknowledgments

The help of the medical doctors, students and scientists who worked in the laboratory (Yi He, Toshiki Uchihara, Marie-Anne Colle, Pascale Lacor, Malika Bennecib, Yolanda Arends, Wienneke Metsaars, Nadège Girardot, Thibaut Lebouvier, Claire Perruchini among others) is greatly acknowledged: as well the expertise of the technical staff. Several studies mentioned in this work were supported by the grants from ANR (ChoAD) and LECMA.

Conflict of interest statement

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Laboratoire de Neuropathologie Escourolle, APHP, Hôpital de La Salpêtrière et Université Pierre et Marie Curie, Paris Universitas, 47 Boulevard de l’Hôpital, 75651, Paris Cedex 13, France

    Charles Duyckaerts

  2. Team 103, Inserm UMRS 975, CNRS UMR 7225, Centre de Recherche Institut du Cerveau et de la Moëlle, Paris, France

    Charles Duyckaerts, Benoît Delatour & Marie-Claude Potier

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  1. Charles Duyckaerts
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  2. Benoît Delatour
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  3. Marie-Claude Potier
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Correspondence to Charles Duyckaerts.

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Duyckaerts, C., Delatour, B. & Potier, MC. Classification and basic pathology of Alzheimer disease. Acta Neuropathol 118, 5–36 (2009). https://doi.org/10.1007/s00401-009-0532-1

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  • DOI: https://doi.org/10.1007/s00401-009-0532-1

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