Prognostic Role of CSF β-amyloid 1–42/1–40 Ratio in Patients Affected by Amyotrophic Lateral Sclerosis

Abstract

The involvement of β-amyloid (Aβ) in the pathogenesis of amyotrophic lateral sclerosis (ALS) has been widely discussed and its role in the disease is still a matter of debate. Aβ accumulates in the cortex and the anterior horn neurons of ALS patients and seems to affect their survival. To clarify the role of cerebrospinal fluid (CSF) Aβ 1–42 and Aβ 42/40 ratios as a potential prognostic biomarker for ALS, we performed a retrospective observational study on a cohort of ALS patients who underwent a lumbar puncture at the time of the diagnosis. CSF Aβ 1–40 and Aβ 1–42 ratios were detected by chemiluminescence immunoassay and their values were correlated with clinical features. We found a significant correlation of the Aβ 42/40 ratio with age at onset and Mini Mental State Examination (MMSE) scores. No significant correlation of Aβ 1–42 or Aβ 42/40 ratios to the rate of progression of the disease were found. Furthermore, when we stratified patients according to Aβ 1–42 concentration and the Aβ 42/40 ratio, we found that patients with a lower Aβ 42/40 ratio showed a shorter survival. Our results support the hypothesis that Aβ 1–42 could be involved in some pathogenic mechanism of ALS and we suggest the Aβ 42/40 ratio as a potential prognostic biomarker.

Targeted proteomics upon Tofersen identifies candidate response markers for SOD1-linked amyotrophic lateral sclerosis

“…Most notably, we found a fraction of markers, namely Aβ42, NfH, NfL, NPY,UCHL1 and GOT1, which not only discriminated SOD1-ALS from controls, but whose levels were also partially "corrected" by the ASO, thus potentially qualifying them as dual diagnostic and therapeutic markers for SOD1-ALS (and possibly also for ALS in general). Consistent with previous studies in sporadic ALS [7][8][9][10], the CSF levels of Aβ42 were increased in SOD1-ALS patients and normalised following treatment with tofersen. Since Aβ40 showed a similar trend, our results reinforce the previously reported interplay between SOD1 and Aβ peptides in ALS [11].…”

Evaluation of Alpha-Synuclein Cerebrospinal Fluid Levels in Several Neurological Disorders

“…Their early identification is crucial, but still today, it is challenging. CSF biomarkers represent precious tools for assessing neurodegenerative disorders providing in vivo information on the underlying pathology [ 21 , 22 , 23 , 24 ]. Specifically, CSF is an ideal biofluid due to its proximity to the brain parenchyma, the moderately low cost in comparison to positron emission tomography imaging, and the safety of lumbar puncture.…”

Neurogranin as a Reliable Biomarker for Synaptic Dysfunction in Alzheimer’s Disease

“…Neurodegenerative diseases are an important health burden and their early identification is crucial, but this is still challenging today. CSF biomarkers represent precious tools for assessing neurodegenerative disorders, providing in vivo information on the underlying pathology [ 23 , 24 , 25 , 26 , 27 ]. Specifically, CSF is an ideal biofluid due to its proximity to the brain parenchyma, the lower intrinsic protease activity than blood, the moderately low cost in comparison to positron emission tomography (PET) imaging and the safety of lumbar puncture.…”