Neurology: The combined effect of synaptic and axon integrity on longitudinal gray matter atrophy in adults with unimpaired cognitive function

Synaptic dysfunction and degeneration are the main features of brain aging, and synaptic preservation buffers can prevent Alzheimer's disease (AD) protein-associated brain atrophy
.
A study published in Neurology tested whether cerebrospinal fluid (CSF) synaptic protein concentrations similarly mitigated the effects of axonal injury on brain atrophy in clinically normal adults, as indicated
by cerebrospinal fluid neurofilament [NFL].

Clinically normal older adults enrolled in the Observational Hillblom Aging Network study at the UCSF Center for Memory and Aging completed baseline lumbar puncture and longitudinal brain MRI (mean scan [follow-up] = 2.
6 [3.
7 years]).

Determination of synaptic proteins (synaptoprotein-1, synaptosome-associated protein 2, neurogranin, growth-associated protein 43 [GAP-43]), axon injury, and AD core biomarkers in cerebrospinal fluid (ptau181/Aβ42 ratio; reflects AD proteinopathy).

10 bilateral temporoparietal gray matter regions of interest sensitive to clinical AD were added to obtain a composite temporoparietal gray matter region
of interest.
The linear mixed-effects model tested the statistical regulation of baseline synaptic proteins on the parietal lobe trajectory associated with baseline β, controlling the ratio
of ptau181/A nf42.

Forty-six clinically normal older adults (mean age = 70 years, 43% of whom were women)
were included.
Synaptic proteins show a small to moderate correlation with NFL (r-range: 0.
10 to 0.
36).

A higher baseline NFL, rather than a Ptau181/Aβ42 ratio, predicts steeper temporoparietal atrophy (NFL x time: β=-0.
08, p<.
001 x>

The relationship between baseline cerebrospinal fluid NfL and longitudinal temporoparietal lobe atrophy is buffered
by synaptic dysfunction acceleration and synaptic integrity.
In addition to AD proteins, simultaneous examination of axonal and synaptic biomarkers in vivo may improve the apparent structural changes
in AD-sensitive brain regions prior to detection.

Source: Saloner R, Fonseca C, Paolillo EW, et al.
Combined Effects of Synaptic and Axonal Integrity on Longitudinal Gray Matter Atrophy in Cognitively Unimpaired Adults [published online ahead of].
print, 2022 Aug 30].
Neurology.
2022; 10.
1212/WNL.
0000000000201165.
doi:10.
1212/WNL.
0000000000201165