Blood Analytes as Biomarkers of Mechanisms Involved in Alzheimer’s Disease Progression

Abstract

Alzheimer’s disease (AD) is the leading cause of dementia, but the pathogenetic factors are not yet well known, and the relationships between brain and systemic biochemical derangements and disease onset and progression are unclear. We aim to focus on blood biomarkers for an accurate prognosis of the disease. We used a dataset characterized by longitudinal findings collected over the past 10 years from 90 AD patients. The dataset included 277 observations (both clinical and biochemical ones, encompassing blood analytes encompassing routine profiles for different organs, together with immunoinflammatory and oxidative markers). Subjects were grouped into four severity classes according to the Clinical Dementia Rating (CDR) Scale: mild (CDR = 0.5 and CDR = 1), moderate (CDR = 2), severe (CDR = 3) and very severe (CDR = 4 and CDR = 5). Statistical models were used for the identification of potential blood markers of AD progression. Moreover, we employed the Pathfinder tool of the Reactome database to investigate the biological pathways in which the analytes of interest could be involved. Statistical results reveal an inverse significant relation between four analytes (high-density cholesterol, total cholesterol, iron and ferritin) with AD severity. In addition, the Reactome database suggests that such analytes could be involved in pathways that are altered in AD progression. Indeed, the identified blood markers include molecules that reflect the heterogeneous pathogenetic mechanisms of AD. The combination of such blood analytes might be an early indicator of AD progression and constitute useful therapeutic targets.

Modern Approaches to the Diagnosis of Cognitive Impairment and Alzheimer’s Disease: A Narrative Literature Review

“…Some authors suggest assessing the levels of iron, ferritin, and cholesterol in the blood as potential markers of cognitive impairment [19] . Other researchers report the potential value of neurogranin as a marker of synaptic dysfunction, the epidermal growth factor (EGF) involved in neurogenesis in adults, as well as pancreatic polypeptide, an increased level of which may be associated with neuronal death [5] .…”

“…The following markers may be used to assess neurodegeneration: a marker for axonal damageplasma neurofilament (NfL); a marker for glial activationglial fibrillary acidic protein (GFAP) [12,13]; β-synuclein [14,15]; visinin-like protein 1 (VILIP-1) [16,17]; and the membrane protein SNAP25 [18]. Some authors suggest assessing the levels of iron, ferritin, and cholesterol in the blood as potential markers of cognitive impairment [19]. Other researchers report the potential value of neurogranin as a marker of synaptic dysfunction, the epidermal growth factor (EGF) involved in neurogenesis in adults, as well as pancreatic polypeptide, an increased level of which may be associated with neuronal death [5].…”

Identification of ULK1 as a novel mitophagy-related gene in diabetic nephropathy

“…In our study, the MRGs were obtained from the Reactome database, which is an emerging database and has been widely used in several studies (65)(66)(67)(68)(69). However, it did not include some mitophagy receptors such as BNIP3, p62, OPTN and so on.…”

Ultrastructural and Molecular Investigation on Peripheral Leukocytes in Alzheimer’s Disease Patients

“…in charge of the local hospital AOUP (Azienda Ospedaliero Universitaria Pisana), were diachronically followed over the past 8 years (from 2014 to 2022). Their clinical data, such as the Clinical Dementia Rating (CDR) score and biochemical values (106 blood analytes), were recorded in a database, as described more in detail by Baldini et al [29]. Each patient was registered with a code and information about their age, sex, and disease onset.…”