Neurogenerative Diseases - 26

Figure 2: pNfH levels in serum as a function of months before the diagnosis of ALS is obtained. Median and interquartile range are given. Kruskal‐Wallis test,
corrected for multiple comparisons (Dunn's post hoc test, ****P < 0.0001, **P < 0.01, *P < 0.05), to compare the prediagnostic ALS groups with the healthy
controls. Adapted from De Schaepdryver et al., 2019.14

colleagues assessed serum pNfH levels in patients
well before the diagnosis of primary sporadic ALS.
Serum pNfH concentrations were elevated up to
18 months prior to the diagnosis of ALS compared
to healthy controls. Furthermore, pNfH levels
continued to rise leading up to diagnosis (Figure 2).
Additionally, a high serum concentration was found
to be associated with a higher risk of death.14

References

Overall, biomarkers that can track neurodegeneration
up to the level of synaptic dysfunction are of
great interest as reliable clinical endpoints in AD
trials. Recently, there have been many biomarkers
proposed for tracking synaptic integrity, but it is
not yet clear which combination of biomarkers has
the highest predictive value. It may be possible
to track neurodegeneration at an early stage by
including biomarkers as clusters including the CSF
beta-amyloids, tau, neurogranin, neurofilaments,
etc. Such studies would provide valuable feedback
regarding mechanisms of action of candidate
therapeutics, as different biofluid biomarkers reflect
different pathophysiological processes in AD.1,10

Merluzzi AP, Vogt NM, Norton D, et al. Differential effects of
neurodegeneration biomarkers on subclinical cognitive decline.
Alzheimers Dement. (N Y). 2019;5:129-138.Jack CR, Jr., Bennett DA,
Blennow K, et al. NIA-AA Research Framework: Toward a biological
definition of Alzheimer's disease. Alzheimers Dement. 2018;14(4):535-
562.

De Vos A, Struyfs H, Jacobs D, et al. The Cerebrospinal Fluid
Neurogranin/BACE1 Ratio is a Potential Correlate of Cognitive
Decline in Alzheimer's Disease. Journal of Alzheimer's disease: JAD.
2016;53(4):1523-1538.

Casaletto KB, Elahi FM, Bettcher BM, et al. Neurogranin, a synaptic
protein, is associated with memory independent of Alzheimer
biomarkers. Neurology. 2017;89(17):1782-1788.

De Vos A, Jacobs D, Struyfs H, et al. C-terminal neurogranin is
increased in cerebrospinal fluid but unchanged in plasma in
Alzheimer's disease. Alzheimers Dement. 2015;11(12):1461-1469.

Portelius E, Zetterberg H, Skillbäck T, et al. Cerebrospinal fluid
neurogranin: relation to cognition and neurodegeneration in
Alzheimer's disease. Brain: a journal of neurology. 2015;138(Pt
11):3373-3385.

Kester MI, Teunissen CE, Crimmins DL, et al. Neurogranin as a
Cerebrospinal Fluid Biomarker for Synaptic Loss in Symptomatic
Alzheimer Disease. JAMA neurology. 2015;72(11):1275-1280.

Vassar R, Bennett BD, Babu-Khan S, et al. β-Secretase Cleavage
of Alzheimer's Amyloid Precursor Protein by the Transmembrane
Aspartic Protease BACE. Science. 1999;286(5440):735-741.

Kirsebom B-E, Nordengen K, Selnes P, et al. Cerebrospinal fluid
neurogranin/β-site APP-cleaving enzyme 1 predicts cognitive
decline in preclinical Alzheimer's disease. Alzheimer's & Dementia:
Translational Research & Clinical Interventions. 2018;4:617-627.

Neurogenerative Diseases

Table of Contents for the Digital Edition of Neurogenerative Diseases