Role of Amyloid from a Multiple Sclerosis Perspective: A Literature Review

Abstract

The traditional concept of multiple sclerosis (MS), that it is primarily a white matter inflammatory disease, has changed a great deal. Thanks to the recent development witnessed in MS research, a whole new idea has emerged that MS is a neurodegenerative disease, and neurodegeneration occurs rather earlier in the pathological process. This has also led to the foundation of the hypothesis that two fundamentally different diseases, Alzheimer's disease (AD) and MS, may share a common mechanism of neurodegeneration. Conventionally, amyloid is thought to be a consequence of protein misfolding and aggregation and is most notorious for its association with debilitating and chronic human diseases. Amyloid is implicated to be related with the deterioration and progression of AD. The finding of amyloid precursor protein expression in axons around the plaque in MS, as well as the correlation of amyloid-β (Aβ) with different stages of MS, has clearly indicated that amyloid plays some kind of key role in MS disease pathogenesis. Excitingly, a paradoxical phenomenon of Aβ has also been observed in several studies recently. It has been shown that amyloid might actually be helping in ameliorating the inflammatory effect in diseases like AD and MS. Amyloid imaging allows earlier diagnosis of MS by taking advantage of the relation of amyloid with MS. This will have a big impact on patient diagnosis and management. In this review I have included the findings of research studies dating from several years back to the most recent ones. Through this review I have tried to show the critical role of amyloid in MS and the importance of investigating through PET imaging.

CSF Aβ42/Aβ40 and Aβ42/Aβ38 ratios: better diagnostic markers of Alzheimer disease

“…The ratios increased the classification performance both for people who were falsely classified as positive (by low CSF A β 42) and for people who were falsely classified as negative (by high CSF A β 42). In line with our findings, a positive correlation between the CSF A β 38/A β 42 ratio and cortical amyloid load (assessed with Pittsburgh compound B PET) has been reported in cognitively healthy individuals …”

“…It might be that subcortical pathologies not specific to AD cause reduced levels of CSF A β 42. Some studies have found low CSF A β 42 levels in multiple system atrophy and multiple sclerosis . In this study, we show that in patients with mild cognitive complaints, low CSF A β 42, A β 40, and A β 38 were all linked to subcortical injury, including increased white matter lesions and enlarged lateral ventricles.…”

A new frontier for amyloid PET imaging: multiple sclerosis

“…The possibility of using PET imaging with tracers for myelin dynamics in MS patients has also been investigated in recent years. 11 C-1,4-bis(p-Aminostyryl)-2-methoxybenzene (BMB) was the first tracer used for PET imaging of myelin [20]. The tracer shows high affinity for WM, but the its slow kinetics means that a longer acquisition time is required that is not feasible given the short half-life of 11 C (20 min) [20].…”

“…11 C-1,4-bis(p-Aminostyryl)-2-methoxybenzene (BMB) was the first tracer used for PET imaging of myelin [20]. The tracer shows high affinity for WM, but the its slow kinetics means that a longer acquisition time is required that is not feasible given the short half-life of 11 C (20 min) [20]. Another myelin PET tracer, N-[ 11 C]methyl-4,4′diaminostilbene ( 11 C-MeDAS ), has been evaluated in wildtype and transgenic hypermyelinated mice (Plp-AktDD) [20].…”

Sequence-to-Structure Relation in Proteins-Amyloidogenic Proteins with Chameleon Sequences

“…When amyloidogenesis involves long polypeptide chains (unlike prions, which tend to be short), the end result is typically a mass of elongated fibrils which disrupt the functioning of otherwise healthy tissue [21][22][23][24].…”