Dementia in
Alzheimer's disease (AD) is ultimately due to cell loss mediated by several mechanisms including, apoptosis, impaired mitochondrial function, and possibly
necrosis. A second major neuroanatomic correlate of
dementia is aberrant cortical neuritic sprouting with abundant proliferation of dystrophic neurites. Early in vivo detection of AD will require non-invasive assays of highly sensitive and relatively specific
biomarkers that reflect these fundamental abnormalities in cellular function. The AD-associated neuronal thread
protein (AD7c-NTP) gene encodes an approximately 41 kD membrane-spanning
phosphoprotein that causes apoptosis and neuritic sprouting in transfected neuronal cells. The
AD7c-NTP gene is over-expressed in AD beginning early in the course of disease. In the brain, increased
AD7c-NTP immunoreactivity is associated with phospho-tau-immunoreactive cytoskeletal lesions, but not with
amyloid-? accumulations. The levels of
AD7c-NTP in postmortem brain tissue correlate with the levels measured in paired ventricular fluid samples, suggesting that the
protein is secreted or released by dying cells into cerebrospinal fluid (CSF). In this regard, elevated levels of
AD7c-NTP can be detected in both CSF and urine of patients with early or moderately severe AD, and the CSF and urinary levels of
AD7c-NTP correlate with the severity of
dementia. The newest configuration of the
AD7c-NTP assay, termed "7c
Gold", has greater than 90% sensitivity and specificity for detecting early AD. The aggregate results from a number of studies suggest that
AD7c-NTP is an excellent
biomarker that could be helpful in the routine clinical evaluation of elderly patients at risk for AD.