2025 Hyper Recent •CC0 1.0 Universal

This work is dedicated to the public domain. No rights reserved.

Access Preprint From Server
September 7th, 2025
Version: 1
University of Miami Miller School of Medicine: University of Miami School of Medicine
neuroscience
bioRxiv

Disrupted Lipid Homeostasis as a Pathogenic Mechanism in ABCA7-Associated Alzheimers Disease Risk

Pericak-Vance, M. A.Open in Google Scholar•Nam, Y.Open in Google Scholar•DeRosa, B. A.Open in Google Scholar•Ramirez, A. M.Open in Google Scholar•Ayele, B. A.Open in Google Scholar•Whitehead, P. G.Open in Google Scholar•Adams, L. D.Open in Google Scholar•Golightly, C. G.Open in Google Scholar•Starks, T. D.Open in Google Scholar•Laverde-Paz, J.Open in Google Scholaret al.

INTRODUCTION: ABCA7 (ATP-binding cassette sub-family A member 7) encodes a lipid transporter linked to Alzheimers disease (AD). While common variants confer modest risk in Europeans, a 44-base pair deletion (rs142076058; p.Arg578Alafs) is a strong risk factor in African Americans (AA). Despite this, the biological consequences of this ancestry-specific variant are not well understood. METHODS: We expressed the truncated ABCA7 protein in HEK and HepG2 cells to assess localization and lipid metabolism. Additionally, induced pluripotent stem cell (iPSC)-derived neurons carrying the deletion were compared with isogenic controls. RESULTS: The truncated ABCA7 localized to the plasma membrane similarly to wild type but induced significant lipid droplet accumulation in HepG2 cells and iPSC-derived neurons. DISCUSSION: These findings show that the AA-specific ABCA7 deletion disrupts lipid regulation despite normal localization, suggesting a mechanistic link between impaired lipid homeostasis and increased AD risk. This work underscores the importance of ancestry-specific studies in AD research.

Similar Papers

bioRxiv
Mon Sep 08 2025
NERV: A Comprehensive Framework for Rapid, Reproducible, and Hardware-Synchronized Neuroscience Experiment Design and Execution
Background: Behavioral neuroscience experiments require precise stimulus control, millisecond timing, hardware integration, and robust data provenance. Increasing use of 3D environments and multimodal recordings adds challenges for development, accessibility, and reproducibility. Fragmented tools often separate presentation, synchronization, and logging, leading to inefficiencies. New Method: The ...
Coutray, K.
•
Constantinidis, C.
bioRxiv
Mon Sep 08 2025
Immersive NREM dreaming preserves subjective sleep depth against declining sleep pressure
Perceived sleep depth is a key determinant of subjective sleep quality, traditionally thought to reflect unconsciousness and reduced cortical activation. Here, we combined high-density EEG with a serial awakening paradigm during NREM sleep to examine its neural and experiential correlates. As expected, deeper sleep was associated with reduced cortical activation, reflected in a lower high-to-low f...
Michalak, A.
•
Marzoli, D.
•
Pietrogiacomi, F.
•
Bergamo, D.
...•
Bernardi, G.
bioRxiv
Mon Sep 08 2025
Distortion rules: audibility creation in the mosquito ear
Hearing begins when ears convert sound into neuronal excitation. The hearing organs of male Anopheles mosquitoes rank amongst the most sensitive ears evolved. Males use them to detect faint female flight tones within noisy mating swarms, but female flight tones largely lie above the male's hearing range. We report a mechanism by which inaudible higher-frequency primary tones become audible through...
Alampounti, C. A.
•
Georgiades, M.
•
Faber, J.
•
Bagi, J.
...•
Albert, J.
bioRxiv
Mon Sep 08 2025
A Novel Mechanism for Tauopathy in Progressive Multiple Sclerosis: Excitotoxic Misplacement of a Mitochondrial Anchor into Dendrites Driven by Tau-hyperphosphorylation
On April 2nd, 2025, the FDA approved a Fast Track Designation for Biogen to use Antisense Oligonucleotides (ASO) to treat tauopathy in clinical trials for Alzheimer Disease (AD) to meet an unmet medical need [1]. For Multiple Sclerosis (MS), there is a similar unmet medical need regarding tauopathy when MS transitions into the late, or Progressive MS that is currently incurable. AD and MS share co...
Chiu, S. Y.
•
Ploski, J. E.
•
Joshi, D. C.
•
Zhang, C.
•
Mathur, D.
bioRxiv
Mon Sep 08 2025
Motor cortex flexibly deploys a high-dimensional repertoire of subskills
Skilled movement often requires flexibly combining multiple subskills, each requiring dedicated control strategies and underlying computations. How the motor system achieves such versatility remains unclear. Using high-density Neuropixels recordings from primary motor cortex (M1) in macaques performing a challenging force-tracking task, we reveal that M1 activity is much higher-dimensional, and fa...
Amematsro, E. A.
•
Trautmann, E. M.
•
Marshall, N. J.
•
Abbott, L.
...•
Churchland, M. M.
bioRxiv
Mon Sep 08 2025
Cortex-wide alignment to the temporal structure of smartphone interactions
Smartphone use varies ranging from rapid, rhythmic tapping (e.g., texting) to slower, irregular scrolling (e.g., browsing), resulting in diverse patterns of inter-touch intervals. The underlying brain processes may dynamically align to these patterns. We investigated brain signals captured by using EEG during hour long smartphone use sessions (n = 53 subjects, accumulating 136,869 interactions). W...
Wan, W.
•
Ghosh, A.
bioRxiv
Mon Sep 08 2025
Astrocytes mobilize a broader repertoire of lysosomal repair mechanisms than neurons
Lysosomal damage impairs proteostasis and contributes to neurodegenerative diseases, yet cell-type-specific differences in lysosomal repair remain unclear. Using a neuron-astrocyte coculture system, we compared responses to lysosomal injury induced by a lysosomotropic methyl ester. Both neurons and astrocytes showed lysosomal damage, marked by galectin-3 recruitment to lumenal lysosomal beta-galac...
Smith, E. M.
•
Chanaday, N. L.
•
Maday, S.
bioRxiv
Mon Sep 08 2025
A multimodal human-computer interaction dataset for neurocognitive user state evaluation
We introduce the Simulated Environment for Neurocognitive State Evaluation (SENSE-42), a multimodal dataset collected during user interactions with desktop computers. It is designed for studying spontaneous fluctuations in the neurocognitive state related to the tonic alertness of computer users, with recordings from 42 participants over 2-hour sessions. Within a simulated desktop environment, par...
Zhang, S.
•
Bai, X.
•
Hartley-O'Dwyer, C.
•
Warren, H.
...•
Noreika, V.
bioRxiv
Mon Sep 08 2025
Using time-resolved auditory frequency tagging to capture self-preferential processing of the own (vs other) name
The own name is an important, salient self-related stimulus and ostensive cue. Prioritized processing of ones own name plays a key role in attention, self-awareness, and social and cognitive development. Previous studies using event-related potentials (ERPs) have reported a self-preferential effect for the own name, characterized by enhanced neural responses compared to the names of (close) others...
Oomen, D.
•
Cracco, E.
•
Nijhof, A. D.
•
Wiersema, J. R.
bioRxiv
Mon Sep 08 2025
Evidence for hierarchical representations of written and spoken words from an open-science human neuroimaging dataset
Reading and speech recognition rely on multi-level processing that builds from basic visual or sound features to complete word representations, yet details of these processing hierarchies (in particular those for spoken words) are still poorly understood. We re-analyzed the functional magnetic resonance imaging (fMRI) data provided in the Mother Of all Unification Studies (MOUS) open-science datas...
Banerjee, S.
•
Jin, K.
•
Nikolov, P.
•
Cho, P.
...•
Riesenhuber, M.