Neurogenerative Diseases - 22

The New Biofluid
Biomarkers in Town
There is increasing demand to identify synaptic proteins as staging
biomarkers capable of predicting the onset of cognitive decline and/
or course of disease.
Philipp Arendt and Iswariya Venkataraman
The need for early intervention in Alzheimer's disease
(AD) could be addressed by having biomarkers that
can reliably predict cognitive decline before the
onset of clinical symptoms.1 Recently, the National
Institute on Aging and the Alzheimer's Association
released a research framework that emphasizes the
implementation of biomarkers in the diagnosis of
people with Alzheimer's disease. The amyloid, tau,
and neurodegeneration (ATN) classification system
recommends the measurement of cerebrospinal
fluid (CSF) biomarkers beta-amyloid (Aβ42) or
the Aβ42/Aβ40 ratio for evaluating amyloidosis,
phosphorylated tau (P-tau) for neurofibrillary
tangles, and total-tau (T-tau) for estimating
neurodegeneration.2 However, CSF Aβ and P-tau are
markers for establishing disease state and possess
limited prognostic value with regards to determining
onset of cognitive decline or monitoring its
progression. Therefore, there is increasing demand
to identify synaptic proteins as staging biomarkers
capable of predicting the onset of cognitive
decline and/or course of disease.3 Furthermore, the
ATN research framework recommends exploring

other biomarkers for neurodegeneration such
as neurogranin or neurofilament light chain to
effectively predict cognitive decline.2

Neurogranin
Neurogranin is a post-synaptic protein, critical for
long-term potentiation signaling in neurons. In AD,
neurogranin levels are decreased in the brain and
increased in the CSF and correlate to a lesser extent
with CSF tau and amyloid.4,5 Additionally, elevated
baseline CSF neurogranin levels correlated well with
rapid declines in cognition, hippocampal volumes,
and cortical glucose metabolism in patients with
mild cognitive impairment (MCI) and AD.6 Kester and
colleagues assessed the role of neurogranin in the
diagnosis, prognosis, and monitoring of AD. In this
study, baseline CSF neurogranin levels were elevated
in AD patients compared with subjects with normal
cognition. Additionally, baseline neurogranin
concentrations were higher in MCI patients who
advanced to AD compared with MCI patients who
did not progress to dementia.

22
Neurogenerative Diseases

Table of Contents for the Digital Edition of Neurogenerative Diseases
