The standardization of cerebrospinal fluid markers and neuropathological diagnoses brings to light the frequent complexity of concomitant pathology in Alzheimer's disease: The next challenge for biochemical markers?

Clin Biochem 2019 Oct 10;72:15-23. Epub 2019 Jun 10.

Institut de Pathologie Est -Neuropathologie, Hospices civils de Lyon, Lyon, France; University Claude Bernard Lyon 1, Lyon, France; Department of Cancer Cell Plasticity, Cancer Research Centre of Lyon, INSERM U1052, CNRS UMR5286, Lyon, France. Electronic address:

During the last two decades, neuropathological examination of the brain has evolved both technically and scientifically. The increasing use of immunohistochemistry to detect protein aggregates paralleled a better understanding of neuroanatomical progression of protein deposition. As a consequence, an international effort was achieved to standardize hyperphosphorylated-Tau (phospho-TAU), ßAmyloid (Aß), alpha syncuclein (alpha-syn), phosphorylated transactive response DNA-binding protein 43 (phospho-TDP43) and vascular pathology detection. Meanwhile harmonized staging systems emerged in order to increase inter rater reproducibility. Therefore, a refined definition of Alzheimer's disease was recommended., a clearer picture of the neuropathological lesions diversity emerged secondarily to the systematic assessment of concomitant pathology highlighting finally a low rate of pure AD pathology. This brings new challenges to laboratory medicine in the field of cerebrospinal fluid (CSF) markers of Alzheimer's disease: how to further validate total Tau, phospho-TAU, Aß40 and Aß42 and new marker level cut-offs while autopsy rates are declining?

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http://dx.doi.org/10.1016/j.clinbiochem.2019.06.004DOI Listing
October 2019

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