I am reminded of the 1994 paper by Mirra et al. that compared neuropathological assessments of sections from AD brains and concluded "quantitative measures yielded significant differences between raters for plaque and tangle counts (p <0.0001). These differences reflected variation in stain sensitivity, staining technique (even when the same stain was used), and interpretation of the histological findings." Now, in this paper by Alafuzoff et al., the evidence seems to support the general findings of the earlier Mirra et al. study by saying "even when only one antibody was used, the type of Aβ-aggregates (diffuse/cored), type of vessel and Vonsattel grade, were not reliably assigned. Furthermore, the quantification of lesions was far from reliable…the agreement while assessing density (some, moderate and many) was unimpressive." However, contrary to the evidence presented in the abstract, Alafuzoff et al. state, "In conclusion, we can confirm the utility of immunohistochemical detection of Aβ-protein in diagnostics and research."

Both these studies indicate less than...  Read more

I am reminded of the 1994 paper by Mirra et al. that compared neuropathological assessments of sections from AD brains and concluded "quantitative measures yielded significant differences between raters for plaque and tangle counts (p <0.0001). These differences reflected variation in stain sensitivity, staining technique (even when the same stain was used), and interpretation of the histological findings." Now, in this paper by Alafuzoff et al., the evidence seems to support the general findings of the earlier Mirra et al. study by saying "even when only one antibody was used, the type of Aβ-aggregates (diffuse/cored), type of vessel and Vonsattel grade, were not reliably assigned. Furthermore, the quantification of lesions was far from reliable…the agreement while assessing density (some, moderate and many) was unimpressive." However, contrary to the evidence presented in the abstract, Alafuzoff et al. state, "In conclusion, we can confirm the utility of immunohistochemical detection of Aβ-protein in diagnostics and research."

Both these studies indicate less than desirable reliability in the neuropathological assessment of AD. Might it be time to minimize reliance on the lesions described more than 100 years ago by Alzheimer and develop more reliable methods, perhaps using molecular techniques?

References:
Mirra SS, Gearing M, McKeel DW, Crain BJ, Hughes JP, van Belle G, Heyman A. Interlaboratory comparison of neuropathology assessments in Alzheimer's disease: a study of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) J Neuropathol Exp Neurol. 1994 May;53(3):303-15. Abstract Erratum appears in J Neuropathol Exp Neurol 1994 Jul;53(4):425. Comment in: J Neuropathol Exp Neurol. 1995 Jan;54(1):129-31; Journal of Neuropathology & Experimental Neurology. 1994 53(3):303-15.

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