Unbiased cerebrospinal fluid proteomics identify coordinated increases in HDL-like lipid transport proteins and myelination pathways following investigational Spectris™ sensory stimulation

Cognito Therapeutics, a clinical-stage neurotechnology company developing novel therapies for neurodegenerative disorders, today announced the presentation of new exploratory biomarker data at the Alzheimer's Association International Conference (AAIC) 2026 highlighting a potential biological mechanism underlying the company's investigational Spectris™ neuromodulation platform.

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Cognito Spectris-AD investigational device. Image credit: Cognito Therapeutics

The poster presentation, titled “Spectris™ Sensory Stimulation Increases CSF HDL-Like Lipid Transport Proteins in Alzheimer's Disease,” reports exploratory cerebrospinal fluid (CSF) proteomics findings from the Phase 2 FLICKER study evaluating daily Spectris™ sensory stimulation in patients with amyloid-positive mild cognitive impairment (MCI).

Using an unbiased, mass spectrometry-based proteomics analysis, investigators found that daily Spectris treatment increased CSF levels of multiple HDL-like lipid transport proteins, including APOA1, APOA2 and APOL1. Pathway analysis further demonstrated that 13 of the 29 significantly upregulated biological pathways were associated with lipid transport or metabolism, suggesting a coordinated biological response rather than isolated protein changes.

The analysis also identified significant enrichment of the Oligodendrocyte/Myelination (M36) co-expression module, a pathway associated with myelin integrity and white matter biology. These findings are consistent with previously reported MRI observations from Cognito's OVERTURE feasibility study suggesting preservation of white matter and myelin following Spectris treatment.

“Every new dataset helps us build a more complete understanding of how non-invasive neuromodulation may impact the biology of Alzheimer's disease,” said Christian Howell, Chief Executive Officer, Cognito Therapeutics. “The unbiased identification of coordinated lipid transport and myelination pathways is an encouraging finding that reinforces our scientific hypothesis and expands our understanding of Spectris' potential mechanism of action. Although these analyses are exploratory, they provide an important rationale for evaluating these biomarkers in future clinical studies as we continue advancing a new category of neuroprotective therapies.”

The findings are particularly notable because the lipid transport proteins were identified through an unbiased proteomics screen. APOA1 has previously been associated with Alzheimer's disease biology, with published studies demonstrating an inverse relationship between CSF APOA1 levels and phosphorylated tau (pTau181), further supporting the biological relevance of this pathway.

The exploratory analyses included 10 amyloid-positive MCI participants enrolled in the Phase 2 FLICKER study. Participants received one hour of daily Spectris treatment for either eight weeks or four weeks using a delayed-start design. CSF samples collected at baseline, four weeks and eight weeks were analyzed using unbiased tandem mass spectrometry to characterize treatment-related changes in protein expression. The data support further evaluation of lipid transport and myelination biomarkers as pre-specified endpoints in future, adequately powered clinical trials.

About Cognito Therapeutics

Cognito Therapeutics is a late clinical-stage neurotechnology company pioneering neuroprotective therapies to address the unmet needs of patients living with CNS disorders and support broader brain health. Its lead product, Spectris™, is an investigational at-home neuroprotective therapy platform that uses non-invasive, sensory-driven neurostimulation to evoke gamma frequency brain activity. The company’s feasibility studies have shown the potential for Spectris to preserve cognition, daily function, and slow brain atrophy in patients diagnosed with mild-to-moderate AD. Cognito is headquartered in Cambridge, MA. For more information, visit www.cognitotx.com and follow @cognitotx.

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