Neurogenerative Diseases - 24

Therefore, neurogranin is a promising progressionpredictive biomarker in AD, and elevated levels might
indicate presymptomatic synaptic dysfunction.7 The
potential role of neurogranin as an AD CSF biomarker
was shown by De Vos and colleagues. A significant
increase in CSF neurogranin levels was observed in
patients with MCI, AD, and those with elevated T-tau
levels compared with cognitively healthy subjects.
CSF neurogranin showed a positive correlation with
CSF T-tau, but it correlated negatively with the CSF
Aβ42/Aβ40 ratio, suggesting that both CSF T-tau and
neurogranin could be markers of synaptic damage.5

compared with single analytes including CSF T-tau,
Aβ42, Aβ40, and Aβ38 in AD.3 The potential value of
the CSF neurogranin/BACE1 ratio has been further
elaborated and confirmed in early stages of AD.9
Schaeverbeke et al. showed that CSF biomarkers
including neurogranin, BACE1, Aβ42, and Aβ38 as well
as markers of innate immunity correlated with
reduced gray matter volume and increased amyloid
load in the precuneus in cognitively normal older
subjects. It has been shown that atrophy in the
precuneus could be observed 3-5 years prior to the
diagnosis of AD in asymptomatic subjects and in
patients with amnestic MCI. Therefore, evaluating
biomarkers of synaptic integrity such as neurogranin
would be useful in tracking the underlying
neurodegenerative process in asymptomatic
subjects who are at risk of progressing to AD.10
Another study showed that CSF neurogranin levels
were significantly elevated only in AD patients
but not in other neurodegenerative conditions,
suggesting that CSF neurogranin along with classical
biomarkers such as the CSF P-tau and Aβ42/Aβ40
ratio could potentially be used for the differential
diagnosis of AD.11

In 2016, a novel immunoassay was designed by ADx
NeuroSciences, Belgium, that specifically targeted
neurogranin, a C-terminally truncated 75-residue
fragment (neurogranin trunc P75, hereafter referred
to as neurogranin), as this is more abundant than the
intact C-terminus fragment in the CSF.3 This assay was
later validated and commercialized by EUROIMMUN
AG, Germany. The added diagnostic value of the
ratio of neurogranin/beta-secretase 1 (BACE1) to
the classical biomarkers in AD was assessed by De
Vos and colleagues.3 BACE1 is the transmembrane
aspartyl protease that causes the production of toxic
Aβ42 aggregates.8 De Vos et al. showed that CSF
neurogranin/BACE1 ratio significantly correlated
with longitudinal reductions in Mini-Mental State
Examination (MMSE) scores in MCI and AD patients.
An elevated CSF neurogranin/BACE1 ratio predicted
a faster decline in MMSE scores, suggesting that this
ratio could potentially be a marker of progression in
AD. No such correlations were observed with other
classical AD biomarkers such as CSF tau or Aβ, neither
as single analytes nor as ratios. Additionally, the
levels of both CSF neurogranin and BACE1 increased
when progressing from cognitively normal to MCI
and subsequently decreased when progressing to
AD (Figure 1). In short, the neurogranin/BACE1 ratio
demonstrated a higher diagnostic performance

Phosphorylated neurofilament
heavy chain
Neurofilaments (Nf ) are up-and-coming star
analytes in neurology. They are gaining increasing
attention as highly specific biomarkers for axonal
damage in neurodegenerative, inflammatory,
vascular, and traumatic diseases. They are regarded
as promising biomarkers because they can indicate
the presence of acute and chronic neuroaxonal
damage independent of the underlying pathological
process. Nfs are predominantly elevated in rapidly
progressing neurodegenerative diseases such as
prion and motoneuron diseases (MND) but also in

24
Neurogenerative Diseases

Table of Contents for the Digital Edition of Neurogenerative Diseases
