Neuroimaging and psychometrics, I predict, will be routinely used in the future. Personally I think CSF testing will efficacious but unnecessary with less invasive methods available. Genetics - no.

View all comments by J. Lucy Boyd

A variable-length polymorphism in the gene TOMM40 predicts the age of late-onset Alzheimer disease.

References:
Roses AD, Lutz MW, Amrine-Madsen H, Saunders AM, Crenshaw DG, Sundseth SS, Huentelman MJ, Welsh-Bohmer KA, Reiman EM. A TOMM40 variable-length polymorphism predicts the age of late-onset Alzheimer's disease. Pharmacogenomics J. 2009 Dec 22. Abstract

View all comments by Allen Roses

The temporal ordering of AD biomarkers is coming into sharper focus through a number of multicenter biomarker initiatives and studies, including ADNI. Indeed, as reviewed in a new hypothetical model paper (Jack et al., 2010), studies from ADNI and other centers are providing evidence in support of the hypothesis that the earliest biomarker changes in AD are related to abnormal processing of Aβ that lead to reduced CSF Aβ42 levels and brain deposits of Aβ in amyloid plaques. This most certainly occurs in subjects who go on to develop AD but who are still cognitively normal when these early events take place.

Thus, as hypothesized by ADNI investigators in Jack et al., the earliest biomarkers that reflect onset of AD pathology (but not necessarily clinical manifestations of AD) are reductions in CSF Aβ42 and PIB-PET positivity.

This is followed by the dysfunction and degeneration of neurons as reflected in changes in biomarkers of neuronal injury and neurodegeneration, including increased levels of CSF tau and cerebral atrophy demonstrated by MRI. These events also are...  Read more

The temporal ordering of AD biomarkers is coming into sharper focus through a number of multicenter biomarker initiatives and studies, including ADNI. Indeed, as reviewed in a new hypothetical model paper (Jack et al., 2010), studies from ADNI and other centers are providing evidence in support of the hypothesis that the earliest biomarker changes in AD are related to abnormal processing of Aβ that lead to reduced CSF Aβ42 levels and brain deposits of Aβ in amyloid plaques. This most certainly occurs in subjects who go on to develop AD but who are still cognitively normal when these early events take place.

Thus, as hypothesized by ADNI investigators in Jack et al., the earliest biomarkers that reflect onset of AD pathology (but not necessarily clinical manifestations of AD) are reductions in CSF Aβ42 and PIB-PET positivity.

This is followed by the dysfunction and degeneration of neurons as reflected in changes in biomarkers of neuronal injury and neurodegeneration, including increased levels of CSF tau and cerebral atrophy demonstrated by MRI. These events also are associated with synaptic dysfunction, as evidenced by abnormalities on FDG-PET.

Thus, as summarized in Jack et al., ADNI investigators propose a model relating disease stage to AD biomarkers in which 1) Aβ amyloid biomarkers become abnormal first, before neurodegenerative biomarkers and before cognitive symptoms, and 2) neurodegenerative biomarkers become abnormal later and correlate with clinical symptom severity. The timing of these varies in single patients for reasons reflecting genetic and environmental factors that increase or decrease an individual's resilience in response to progressive accumulations of AD pathologies. Still, the available data is best interpreted to support the temporal sequence or ordering of AD biomarkers described above and in Jack et al.

References:
Jack Jr, C.R., Knopman, D.S., Jagust, W.J., Shaw, L.M., Aisen, P., Weiner, M.W., Petersen, R.C., and Trojanowski, J.Q. Hypothetical model of dynamic biomarkers of the Alzheimer’s pathological cascade. Lancet Neurol., 9:119-128, 2010.

View all comments by John Trojanowski