Alzheimer’s disease (AD) is the most common neurodegenerative disorder and a leading cause of dementia. One major challenge for clinicians is accurately assessing the rate of disease progression (RoP) early in the diagnostic process, which is crucial for patient management and clinical trial stratification. This study evaluated the role of cerebrospinal fluid biomarkers—Aβ42, t-Tau, pTau, Neurogranin (Ng), and Neurofilament light-chain (NF-L)—in predicting RoP at the time of AD diagnosis. We included 56 AD patients and monitored cognitive impairment using MMSE scores at diagnosis and during six-month follow-up visits. RoP scores were calculated based on these assessments. Our correlation analyses revealed significant associations between RoP and pTau, Aβ42/Ng ratio, and NF-L levels. When patients were stratified by median RoP values into low-to-moderate (L-M: 2) groups, those in the U-M group had notably higher CSF NF-L levels compared to the L-M group. Logistic regression analysis further demonstrated that elevated CSF NF-L levels were predictive of a faster RoP. These findings highlight the potential of CSF NF-L as a prognostic biomarker for rapid disease progression in AD. By identifying patients at risk for accelerated cognitive decline, CSF NF-L could significantly enhance early intervention strategies and improve patient management in clinical settings.

VPS13A disease is a rare, autosomal-recessive, neurodegenerative disorder characterized by involuntary movements, orofacial dystonia, seizures, psychiatric symptoms, and the presence of spiky, deformed red blood cells (acanthocytes). The disease is caused by mutations in the VPS13A gene, which encodes the VPS13A protein (previously known as chorein). This protein is a member of the family of bridge-like lipid transport proteins, involved in bulk lipid transfer between membranes and intracellular vesicle trafficking. We describe the case of a 37-year-old woman with gait instability, semi-flexed legs, and involuntary distal muscle movements. Genetic testing was performed using next-generation sequencing (NGS), followed by molecular analysis. Fibroblasts from the patient, her mother, and a healthy control were analyzed by immunofluorescence and Western blotting. NGS identified a novel homozygous 2.8 kb deletion encompassing exons 69–70 (69–70del) of the VPS13A gene (NM_033305.3). The same variant was detected in the patient’s mother in a heterozygous state and her brother in a homozygous state. Although other deletions in the gene have been described, a comprehensive search of population variant databases and the existing literature did not reveal previous reports of this deletion. Fibroblasts from the patient, her mother and a healthy control were characterized. Functional assays showed a complete absence of the VPS13A protein in the patient’s fibroblasts. This study expands the mutational spectrum of VPS13A-linked VPS13A disease and underlines the importance of comprehensive genetic analysis in atypical cases.