Alzheimer’s Disease

Changes in Amyloid-β and Tau in the Cerebrospinal Fluid of Transgenic Mice Overexpressing Amyloid Precursor Protein

Science Translational Medicine  17 Jul 2013:
Vol. 5, Issue 194, pp. 194re2
DOI: 10.1126/scitranslmed.3006446

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From Bedside Back to Bench

The pathology of Alzheimer’s disease (AD) is thought to start 10 to 20 years before the onset of the first clinical symptoms in both sporadic and familial forms of the disease. Thus, disease-modifying drugs will most likely be effective when given at a preclinical stage of disease before neurodegeneration has become severe enough to induce clinical symptoms. Amyloid-β (Aβ) peptide and Tau protein, the constituents of the pathological hallmarks of AD, amyloid plaques and neurofibrillary tangles, respectively, have shown promise as markers in cerebrospinal fluid (CSF) of early, preclinical AD. Transgenic mice overexpressing human amyloid precursor protein (APP) have been used to model Aβ pathology, but CSF markers have not been investigated. To this end, Maia et al. optimized methods for collecting mouse CSF and validated sensitive assays for detecting Aβ peptides and total Tau in mouse CSF. They then used these assays to measure Aβ peptides and total Tau in the CSF of two different APP transgenic mouse models, with different ages of onset and progression of Aβ pathology. They found that the Aβ42 concentration in mouse CSF decreased as Aβ deposition started and that CSF t-Tau increased when amyloid plaques in mouse brain became prominent. Mechanistically, these results suggest that Aβ deposition in the brain may be the driving force for changes in Aβ and Tau in the CSF of AD patients. They also suggest the translational value of APP mouse models for understanding events in human disease.