On 2016 Aug 25, Gerard Ridgway commented:

There is some very interesting discussion of this paper on AlzForum. In particular, Pieter Jelle Visser reports a strong correlation (0.8) between CSF Aβ1-42 and amyloid PET, and David Holtzman notes that CSF Aβ1-42 drops at or before detectable PiB positivity, and that PiB is in turn more sensitive than florbetapir. Another recent paper using ADNI data (Palmqvist S, 2016) also concludes that CSF Aβ1-42 "becomes abnormal in the earliest stages of Alzheimer's disease, before amyloid positron emission tomography and before neurodegeneration".

These results seem strongly discordant with Figure 3 in this paper, which shows florbetapir Aβ deposition occurring second (after vascular abnormalities) and becoming fully abnormal in established LOAD, but CSF Aβ1-42 abnormalities occurring last (out of 9 biomarkers), and reaching an abnormality level of only about 1/3. If this difference between amyloid PET and CSF Aβ1-42 results is considered implausible, then that could suggest a modelling problem that could also call into question the key finding of early vascular abnormalities.

On 2016 Aug 25, Gerard Ridgway commented:

There is some very interesting discussion of this paper on AlzForum. In particular, Pieter Jelle Visser reports a strong correlation (0.8) between CSF Aβ1-42 and amyloid PET, and David Holtzman notes that CSF Aβ1-42 drops at or before detectable PiB positivity, and that PiB is in turn more sensitive than florbetapir. Another recent paper using ADNI data (Palmqvist S, 2016) also concludes that CSF Aβ1-42 "becomes abnormal in the earliest stages of Alzheimer's disease, before amyloid positron emission tomography and before neurodegeneration".

These results seem strongly discordant with Figure 3 in this paper, which shows florbetapir Aβ deposition occurring second (after vascular abnormalities) and becoming fully abnormal in established LOAD, but CSF Aβ1-42 abnormalities occurring last (out of 9 biomarkers), and reaching an abnormality level of only about 1/3. If this difference between amyloid PET and CSF Aβ1-42 results is considered implausible, then that could suggest a modelling problem that could also call into question the key finding of early vascular abnormalities.