Abstract Details

Title Circadian trends in CSF Amyloid beta-42 levels in HIV

Topic Infectious Disease

Presentation(s) S38 - All Things HIV and ID (4:18 PM-4:30 PM)

Poster/Presentation
Number 005

Background Ab42 aggregates to form neurotoxic extracellular plaques in brain parenchyma, likely contributing to neurocognitive impairment in disorders such as Alzheimer’s disease. Ab42 is cleared from brain parenchyma through the glymphatic system. This clearance increases during normal sleep, and is associated with diurnal fluctuations such that CSF Ab42 levels are lowest in the morning, and increase during wakefulness. However, sleep disturbances in the context of HIV infection may disrupt this diurnal pattern.

Objective To study circadian patterns in cerebrospinal fluid (CSF) amyloid beta-42 (Ab42) levels in people with HIV (PWH), we measured CSF biomarkers over various time points in the day.

Design/Methods We performed lumbar punctures in virally suppressed PWH. The fully automated Simoa platform was used to measure CSF biomarkers, including total tau (T-tau), phosphorylated tau (pTau181), A b42, and Ab40. CSF total protein was measured by standard methods in a CLIA-certified lab. Neurocognitive (NC) performance was summarized using the global deficit score (GDS).

Results

Participants were 256 PWH, 16.4% female, 16.1% Black, 7.5% Hispanic, 61.4% non-Hispanic white, and 15% other race/ethnicities, mean (SD) age 56.5 (6.5) years. Median (interquartile range) current and nadir CD4+ T-cells were 458 (277, 677) and 57 (11, 200), respectively. Average CSF Ab42 levels were lowest in the morning and positively correlated with time over the course of the day (r=0.193, p=0.0127). In comparison, time of day did not significantly influence levels of CSF total protein, Ab40, total Tau, or pTau181. Neither CSF Ab42 (r=0.029; p=0.6420) nor LP time (r=0.0177; p=0.821) were related to NC performance.

Conclusions

Increasing CSF Ab42 levels over the course of the day suggest that diurnal fluctuations are preserved in HIV. However, because participants without HIV were not studied, comparisons of CSF Ab42 levels in PWH with healthy, uninfected individuals are needed to determine the magnitude of alterations in diurnal fluctuations of CSF Ab42 in HIV.

Authors/Disclosures
Visesha Kakarla PRESENTER	Miss Kakarla has nothing to disclose.
Ahmed Chenna, PhD (Monogram Biosciences Inc)	Dr. Chenna has received personal compensation for serving as an employee of LabCorp-monogram Biosciences.
Christos J. Petropoulos, PhD (Monogram Biosciences, LabCorp)	Dr. Petropoulos has received personal compensation for serving as an employee of Monogram Biosciences-Labcorp. Dr. Petropoulos has received stock or an ownership interest from Laboratory Corporation of America Holdings. Dr. Petropoulos has received intellectual property interests from a discovery or technology relating to health care.
	No disclosure on file
	No disclosure on file
	No disclosure on file
John Winslow, PhD (Monogram Biosciences Inc., Laboratory Corporation of America)	Dr. Winslow has received personal compensation for serving as an employee of Monogram Biosciences/Labcorp. Dr. Winslow has stock in Labcorp. Dr. Winslow has received intellectual property interests from a discovery or technology relating to health care.
Erin Sundermann	The institution of Erin Sundermann has received research support from California Department of Public Health.
Scott L. Letendre, MD (HNRC, UCSD)	The institution of Dr. Letendre has received research support from National Institutes of Health. The institution of Dr. Letendre has received research support from University at Buffalo. Dr. Letendre has received publishing royalties from a publication relating to health care.
Ronald J. Ellis, MD, PhD, FAAN (UC San Diego)	Dr. Ellis has nothing to disclose.