Neurology: In the early stage of dementia, related proteins in cerebrospinal fluid can reflect its progress

Synaptic dysfunction is an early process in the pathogenesis of Alzheimer's disease (AD).
Pathological studies have shown that synaptic loss is closely related to cognitive decline
.

Therefore, it is important to further understand the synaptic dysfunction that occurs in the early stages of AD

Some synapse-specific proteins involved in different synaptic pathways can be measured in CSF
.

Among them, the most extensively studied include the postsynaptic protein neurogranin and the presynaptic protein synaptosomal-associated protein-25 (SNAP-25), growth-associated protein-43 (GAP-43) and synaptotagmin-14

Neurogranin is a post-synaptic protein that is highly expressed in the dendritic spines of the hippocampus, amygdala, caudate gland and Putian gland.
It is involved in calcium signal regulation and synaptic plasticity
.

CSF neurogranin can accurately distinguish AD, even in its precursor phase, from healthy controls or other neurological diseases

In the continuous course of preclinical Alzheimer's disease, CSF neurogranin has also been investigated, but the results are conflicting

SNAP-25 is a component of the SNAP receptor (SNARE) complex.
It is located in synaptic vesicles and is essential for the process of cell extravasation
.

Two studies investigated CSF SNAP-25 in patients with preclinical Alzheimer's disease, and no changes in this biomarker were observed

GAP-43 is a presynaptic protein, which is mainly expressed in the hippocampus, endothelium, neocortex, cerebellum, and olfactory bulb.
It is involved in synapses in the adult brain
.

Two studies have shown that CSF GAP-43 increases in preclinical Alzheimer's patients
.

Finally, synaptotagmin-1 is a calcium sensor protein located on the presynaptic plasma membrane, involved in the extravasation of synaptic vesicles and the release of neurotransmitters

Synaptic agmin-1 has not been studied in preclinical Alzheimer's disease
.

In general, previous evidence regarding CSF synaptic biomarkers for preclinical Alzheimer's disease is scarce and unclear

In this way, Marta Milà-Alomà and others of the Brain Research Center (BBRC) in Spain explored whether CSF synaptic biomarkers change in individuals in the preclinical stage of the Alzheimer's continuum
.

Core hypothesis: The level of synaptic biomarkers will change at this early stage
.

In addition, they are also trying to determine whether these synaptic biomarkers are differently associated with AD risk factors and neurodegeneration biomarkers

They conducted a cross-sectional study in the ALFA+ cohort, including middle-aged cognitively accessible participants
.

Using immunoassay measuring protein assay CSF and granulocyte nerve GAP-43, immunoprecipitation Mass Spectrometry Synaptic SNAP-25 and Atlas -1
.
The AD CSF biomarkers Aβ42/40, p-tau and t-tau, and the neurodegeneration biomarker NfL were also measured
.

immunity

Participants underwent structural MRI, as well as fluorodeoxyglucose and Aβ PET imaging
.
A general linear model was used to test the association between CSF synaptic biomarkers and risk factors, Aβ pathology, tau pathology, and neurodegeneration markers
.

All CSF synaptic biomarkers increase with age
.
Females have higher CSF neugranin, while APOE-ε4 carriers have higher CSF SNAP-25
.

All CSF synaptic biomarkers increase with increasing Aβ load (measured by CSF Aβ42/40 and Aβ PET Centiloid values).
Importantly, synaptic biomarkers are even in individuals in the early stages of Aβ deposition Will increase
.

Importantly, synaptic biomarkers increase even in individuals in the early stages of Aβ deposition
.

Higher CSF synaptic biomarkers are also associated with higher CSF p-tau and NfL
.
Higher CSF neurogranin and GAP-43 are related to higher brain metabolism, but lower cortical thickness in brain areas associated with AD
.

The important significance of this study lies in the discovery: CSF synaptic biomarkers increase in the early preclinical stage of the Alzheimer's continuum, even if the pathological burden of Aβ is low, they are related to age, gender, APOE-ε4 and neurodegenerative markers The relationship between things is different
.

CSF synaptic biomarkers increase in the early preclinical stages of the Alzheimer’s continuum,

 

Original Source:
Milà-Alomà M, Brinkmalm A, Ashton NJ, et al.
CSF Synaptic Biomarkers in the Preclinical Stage of Alzheimer Disease and Their Association With MRI and PET: A Cross-sectional Study.
Neurology.
online September 23, 2021: 10.
1212/WNL.
0000000000012853.
doi:10.
1212/WNL.
0000000000012853

CSF Synaptic Biomarkers in the Preclinical Stage of Alzheimer Disease and Their Association With MRI and PET: A Cross-sectional Study.
Neurology.
Leave a message here