Anavex Life Sciences Corp (AVXL)

[Investor2014]

Further to this as other outcome measures we have:

CSF assessment [ Time Frame: 48 weeks ] 
 Changes in CSF parameters (Abeta40, Abeta42, T-tau, P-tau, NFL, YKL-40, neurogranin, BACE1 concentration) characteristic for AD pathophysiology from baseline and compared to placebo at 
  
 +48 weeks treatment differences within subgroups will be performed

This takes the place of PET scans to show differences in subgroups, so here we do have a good selection of potential surrogate endpoint biomarkers including Abeta40 / 42 to flaunt.

Cerebrospinal fluid A beta 1–40 peptides increase in Alzheimer’s disease and are highly correlated with phospho-tau in control individuals

Conclusions
These results indicate that an increase in the baseline level of amyloid peptides, which are associated with an increase in p-tau (181), may be a biological characteristic and possibly a risk factor for AD. Further studies will be needed to establish a causal link between increased baseline levels of Aß40 and the development of the disease.

Plasma and cerebrospinal fluid levels of amyloid beta proteins 1-40 and 1-42 in Alzheimer disease

Results: Mean plasma Abeta40 levels were higher in the AD group than in controls (P = .005), but there was substantial overlap; Abeta42 levels were similar between the groups. Levels of Abeta40 and Abeta42 showed no association with sex or Mini-Mental State Examination scores. There was a significant relationship between age and Abeta40 level in controls but not in the AD group. Levels of Abeta40 were higher in patients with AD with the Apo E epsilon4 allele than in controls (P<.01). Cerebrospinal fluid Abeta40 levels were similar in the AD group and controls. However, Abeta42 levels were lower in the AD group than in controls (P<.001). The levels showed no association with severity of dementia.

Conclusions: Although mean plasma Abeta40 levels are elevated in sporadic AD and influenced by Apo E genotype, measurement of plasma Abeta40 levels is not useful to support the clinical diagnosis of AD. Lower levels of CSF Abeta42 in the AD group are consistent with previous studies.

Total Aß42/Aß40 ratio in plasma predicts amyloid-PET status, independent of clinical AD diagnosis

The good thing is that this Australian study letting us get away with CSF plasma rather than expensive PET scans:

Abstract
Objective To explore whether the plasma total ß-amyloid (Aß) Aß42/Aß40 ratio is a reliable predictor of the amyloid-PET status by exploring the association between these 2 variables in a subset of the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging cohort.

Methods Taking plasma samples at 3 separate time points, month 18 (n = 176), month 36 (n = 169), and month 54 (n = 135), we assessed the total Aß42/Aß40 ratio in plasma (TP42/40) with regard to neocortical Aß burden via PET standardized uptake value ratio (SUVR) and investigated both association with Aß-PET status and correlation (and agreement) with SUVR.

Results The TP42/40 plasma ratio was significantly reduced in amyloid-PET–positive participants at all time points (p < 0.0001). Adjusting for covariates age, gender, APOE e4 allele status, and clinical classification clearly affects the significance, with p values reduced and only comparisons at 54 months retaining significance (p = 0.006). Correlations with SUVR were similar across each time point, with Spearman ? reaching -0.64 (p < 0.0001). Area under the curve values were highly reproducible over time points, with values ranging from 0.880 at 36 months to 0.913 at 54 months. In assessments of the healthy control group only, the same relationships were found.

Conclusions The current study demonstrates reproducibility of the plasma assay to discriminate between amyloid-PET positive and negative over 3 time points, which can help to substantially reducing the screening rate of failure for clinical trials targeting preclinical or prodromal disease.

Classification of evidence This study provides Class II evidence that plasma total Aß42/Aß40 ratio is associated with neocortical amyloid burden as measured by PET SUVR.

So yea an Amyloid Plaques biomarker it is, including using the cheaper plasma version over PET, but likely a chitty one for establishing clinical dementia or the reduction of it as we suspect. But hey the FDA likes it.

If Anavex proves that A2-73 provides effective and clinically meaningful stabilisation or improvement in Alzheimer's Dementia along with reduction in amyloid plaque, the establishment may well completely missing the point claim: "see we told you that amyloid plaques causes AD and removing it helps!".