| 1. |
- Vergallo, A., et al.
(author)
-
Association of plasma YKL-40 with brain amyloid-β levels, memory performance, and sex in subjective memory complainers
- 2020
-
In: Neurobiology of Aging. - : Elsevier BV. - 0197-4580. ; 96, s. 22-32
-
Journal article (peer-reviewed)abstract
- Neuroinflammation, a key early pathomechanistic alteration of Alzheimer's disease, may represent either a detrimental or a compensatory mechanism or both (according to the disease stage). YKL-40, a glycoprotein highly expressed in differentiated glial cells, is a candidate biomarker for in vivo tracking neuroinflammation in humans. We performed a longitudinal study in a monocentric cohort of cognitively healthy individuals at risk for Alzheimer's disease exploring whether age, sex, and the apolipoprotein E ε4 allele affect plasma YKL-40 concentrations. We investigated whether YKL-40 is associated with brain amyloid-β (Aβ) deposition, neuronal activity, and neurodegeneration as assessed via neuroimaging biomarkers. Finally, we investigated whether YKL-40 may predict cognitive performance. We found an age-associated increase of YKL-40 and observed that men display higher concentrations than women, indicating a potential sexual dimorphism. Moreover, YKL-40 was positively associated with memory performance and negatively associated with brain Aβ deposition (but not with metabolic signal). Consistent with translational studies, our results suggest a potentially protective effect of glia on incipient brain Aβ accumulation and neuronal homeostasis. © 2020 Elsevier Inc.
|
|
| 2. |
- Lista, Simone, et al.
(author)
-
Monitoring synaptic pathology in Alzheimer's disease through fluid and PET imaging biomarkers: a comprehensive review and future perspectives
- 2024
-
In: MOLECULAR PSYCHIATRY. - 1359-4184 .- 1476-5578.
-
Research review (peer-reviewed)abstract
- Alzheimer's disease (AD) is currently constrained by limited clinical treatment options. The initial pathophysiological event, which can be traced back to decades before the clinical symptoms become apparent, involves the excessive accumulation of amyloid-beta (A beta), a peptide comprised of 40-42 amino acids, in extraneuronal plaques within the brain. Biochemical and histological studies have shown that overaccumulation of A beta instigates an aberrant escalation in the phosphorylation and secretion of tau, a microtubule-binding axonal protein. The accumulation of hyperphosphorylated tau into intraneuronal neurofibrillary tangles is in turn correlated with microglial dysfunction and reactive astrocytosis, culminating in synaptic dysfunction and neurodegeneration. As neurodegeneration progresses, it gives rise to mild clinical symptoms of AD, which may eventually evolve into overt dementia. Synaptic loss in AD may develop even before tau alteration and in response to possible elevations in soluble oligomeric forms of A beta associated with early AD. These findings largely rely on post-mortem autopsy examinations, which typically involve a limited number of patients. Over the past decade, a range of fluid biomarkers such as neurogranin, alpha-synuclein, visinin-like protein 1 (VILIP-1), neuronal pentraxin 2, and beta-synuclein, along with positron emission tomography (PET) markers like synaptic vesicle glycoprotein 2A, have been developed. These advancements have facilitated the exploration of how synaptic markers in AD patients correlate with cognitive impairment. However, fluid biomarkers indicating synaptic loss have only been validated in cerebrospinal fluid (CSF), not in plasma, with the exception of VILIP-1. The most promising PET radiotracer, [11C]UCB-J, currently faces significant challenges hindering its widespread clinical use, primarily due to the necessity of a cyclotron. As such, additional research geared toward the exploration of synaptic pathology biomarkers is crucial. This will not only enable their extensive clinical application, but also refine the optimization process of AD pharmacological trials.
|
|
| 3. |
- Pomara, N., et al.
(author)
-
Plasma Amyloid-beta dynamics in late-life major depression: a longitudinal study
- 2022
-
In: Translational Psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 12:1
-
Journal article (peer-reviewed)abstract
- Depressed individuals are twice as likely to develop Alzheimer's disease (AD) as compared to controls. Brain amyloid-beta (A beta) deposition is believed to have a major role in AD pathogenesis but studies also suggest associations of A beta dynamics and depression. The aim of this study was to test if plasma A beta levels are longitudinally associated to late-life depression. We measured plasma levels of amyloid-beta(1-40) (A beta 40) and amyloid-beta(1-42) (A beta 42) peptides longitudinally for three consecutive years in 48 cognitively intact elderly subjects with late-life major depressive disorder (LLMD) and 45 age-matched cognitively healthy controls. We found that the A beta 42/A beta 40 plasma ratio was significantly and steadily lower in depressed subjects compared to controls (p < 0.001). At screening, A beta 42/A beta 40 plasma did not correlate with depression severity (as measured with Hamilton Depression Scale) or cognitive performance (as measured with Mini-Mental State Examination) but was associated to depression severity at 3 years after adjustment for age, education, cognitive performance, and antidepressants use. This study showed that reduced plasma A beta 42/A beta 40 ratio is consistently associated with LLMD diagnosis and that increased severity of depression at baseline predicted low A beta 42/A beta 40 ratio at 3 years. Future studies are needed to confirm these findings and examine if the consistently lower plasma A beta 42/A beta 40 ratio in LLMD reflects increased brain amyloid deposition, as observed in AD subjects, and an increased risk for progressive cognitive decline and AD.
|
|
