Steinacker P, Fang L, Kuhle J, Petzold A, Tumani H, Ludolph AC, Otto M, Brettschneider J.
Soluble beta-amyloid precursor protein is related to disease progression in amyotrophic lateral sclerosis.
PLoS One. 2011;6(8):e23600.
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I think that sAPPα and sAPPβ are among the most interesting new biomarkers
for a range of neurodegenerative disorders, including ALS and AD. In line
with their previous report on this topic, Steinacker et al. clearly show
that ALS has a significant impact on sAPP levels in cerebrospinal fluid (CSF). What makes the
present report so interesting is that the results suggest that sAPPs might
serve as accurate predictors of the disease course. This is a highly
relevant topic, since the velocity of disease progression, and therefore the
survival rate, varies from a few months to several years. The results will
surely have to be replicated before they will have a significant impact on
the diagnostic algorithms, but the findings are clearly relevant and promising.
Even though it has been shown that sAPP levels in CSF are also
altered in AD, the reasons are probably different, and I do not think that
the findings offer a link between ALS and AD. sAPP levels are increased in
AD, which is a probably a direct result of faulty Aβ clearance or
overproduction, whereas Steinacker et al. report decreased CSF sAPP levels, probably related to dying neurons, resulting in lower sAPP production. Therefore, I think that sAPP concentration alterations in AD are specific
for the disorder, whereas they are an unspecific phenomenon in ALS. The
specificity of sAPP for AD pathology is probably the most important point;
in my opinion, sAPP will not only be very useful for the early, pre-dementia
diagnosis of AD (and maybe as an unspecific marker of neuronal damage such as
in ALS), but it will also significantly improve the differentiation between
AD versus other non-amyloid dementias such as frontotemporal lobar
degenerations. The feasibility of sAPP measurements in blood, which have
also been shown in the present paper, are of particular interest since they
may provide the means for the first accurate non-invasive biological
diagnostic procedure in this field.
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