​​Focus: The study focused on determining the relationship between age, amyloidosis, and amyloid-beta (Aβ) kinetics in the human central nervous system (CNS).

Method: The study utilized stable isotope labeling kinetics (SILK) to analyze Aβ turnover. Participants received a 9-hour intravenous infusion of leucine to label newly synthesized proteins, including Aβ isoforms. Plasma and CSF samples were collected for 36 hours and the incorporation of labeled leucine into soluble Aβ was quantified. A compartmental model was applied to determine kinetic parameters of Aβ turnover.

Finding: A key finding of the study is that the fractional turnover rate of soluble Aβ peptides in the CNS slows significantly with age.

Limitation: Independent comparisons regarding ApoE allele genotype effects on Aβ kinetics could not be made because ApoE4 was highly associated with amyloidosis, preventing researchers from isolating the specific impact of ApoE on Aβ metabolism before amyloidosis occurred.

​​Focus: Relationship between CSF clearance, Aβ accumulation and cognitive function in individuals with AD.

Method: Two PET tracers to estimate CSF clearance.

Finding: “Ventricular CSF clearance measures were correlated with reductions in Alzheimer’s disease (AD) of 18 and 27% compared to normal.”

Limitation: The absence of direct, non-invasive methods limits understanding of Aβ clearance in humans.

​​Focus: Relationship between CSF clearance, Aβ accumulation and cognitive function in individuals with AD.

Method: Two PET tracers to estimate CSF clearance.

Finding: “Ventricular CSF clearance measures were correlated with reductions in AD of 18 and 27% compared to normal.”

Limitation: The absence of direct, non-invasive methods limits understanding of Aβ clearance in humans.

​​Focus: This study focuses on establishing parenchymal CSF fraction (pCSF) mapping as a sensitive and clinically feasible biomarker for evaluating glymphatic fluid distribution in AD. Ultimately, the research seeks to advance the monitoring of AD and predict responses to treatment by identifying a reliable biomarker for glymphatic clearance.

Method: Retrospective study involved 29 subjects (16 cognitively normal, 13 MCI/AD) who underwent both MRI and C-PiB PET scans. Three MRI-based measures of glymphatic structural alterations were compared. C-PiB PET was used to measure Aβ deposition. The study evaluated cross-correlations among these MRI biomarkers and their respective associations with amyloid deposition via linear regression, adjusting for age and sex.

Finding: Parenchymal CSF (pCSF) mapping demonstrates a significantly stronger positive association with Aβ deposition compared to diffusion-based free-water mapping and perivascular space burden, even after adjusting for age and sex.

Limitation: One study limitation is its cross-sectional nature, which restricts the ability to draw causal inferences between glymphatic dysfunction and the progression of AD. Additionally, the sample size, while adequate for preliminary findings, may not fully capture the nuanced effects of glymphatic clearance across various stages of the disease.

​​Focus: Assessing the structural and vascular alterations of deep cervical lymph nodes (dCLNs) in patients with amyloid PET-positive AD using high-frequency color Doppler ultrasound (HFCDU).

Method: Cross-sectional design involving 25 amyloid PET-positive AD patients and 25 age-matched cognitively normal controls. Participants underwent HFCDU of dCLNs in neck zones 2–5.

Finding: “HFCDU demonstrated distinct morphological and vascular abnormalities of dCLNs in AD, particularly in Zone 5, suggesting impaired lymphatic drainage contributes to AD pathology and supporting lymphatic imaging as a potential biomarker for the failure of lymphatic drainage of the brain.”

Limitation: The study was conducted on a relatively small number of patients at limited stages of AD, which may restrict generalizability.