Alz Res Therapy: Lipocalcin for the diagnosis of dementia

The premortem definition of Alzheimer's disease (AD) has undergone substantial evolution over the past 20 years
.

Cerebrospinal fluid (CSF) biomarkers reflecting AD-related pathological changes, such as CSF phosphorylated tau protein (p-tau) and beta-amyloid 1-42 (Abeta42), and markers of neurodegeneration such as total tau (t-tau) tau), which have been identified, validated, and used as established research criteria for the diagnosis of AD

diagnosis

Recently proposed criteria may even allow a prodromal or preclinical diagnosis if evidence of AD-related Abeta or tau pathology is detected by CSF analysis or positron emission tomography (PET)
.

The next and current focus of biomarker research is to validate minimally invasive tests using plasma or serum

It has recently been reported that assays to detect p-tau, Abeta42, and markers of neural axis damage such as neurofilament light chain (NfL) and elevated t-tau have good diagnostic and prognostic value
.

Beyond this, biomarkers of other aspects of AD pathology, such as neuroinflammation or synaptic damage, are needed to improve diagnosis and monitor specific therapeutic targets in clinical trials

Adiponectin 2 (LCN2), also known as neutrophil gelatin-associated adiponectin, is a secreted glycoprotein involved in innate immunity and brain iron homeostasis, and in the brain in response to injury and inflammation
.

Furthermore, LCN2 mediates hippocampal damage in a vascular dementia (VaD) model, and high CSF LCN2 levels have been reported to be a promising diagnostic biomarker for VaD, whereas CSF LCN2 levels are important in AD-induced mild cognitive impairment ( A decrease was found in patients with MCI)

immune blood vessels

Hereby, Peter Hermann et al at the University of Göttingen aimed to investigate the role of plasma LCN2 in the differential diagnosis of dementia and its use as an independent biomarker by analyzing biomarkers of AD-related pathology and clinical data from AD patients 's utility
.

In addition, differences between normal and rapidly developing AD patients were also assessed to explore potential prognostic utility

They analyzed Lipocalin-2 concentrations in plasma samples from a cohort of n = 407 people in a two-center case-control study
.

The diagnostic group included Alzheimer's disease (n = 74), vascular dementia (n = 28), other important differential diagnoses (n = 221), and healthy controls (n = 84)

They found that: Alzheimer's patients had significantly lower plasma adiponectin-2 compared to healthy controls (p < 0.
001) and all other groups (p < 0.
01), except for mixed dementia (vascular and Alzheimer's disease).
pathological changes in Zheimer's disease)
.

The area under the ROC curve to distinguish Alzheimer's disease from healthy controls was 0.
783 (95% CI: 0.
712-0.
855) in the study cohort and 0.
766 (95% CI: 0.
627-0.
905) in the validation cohort
.

In the study cohort, the area under the curve for Alzheimer's disease and vascular dementia was 0.
778 (95% CI: 0.
667-0.
890)
.

In Alzheimer's disease patients, plasma Lipocalin2 is associated with cerebrospinal fluid biomarkers of neurodegeneration and AD-related pathology (total tau, phosphorylated tau and β-amyloid 1-42), cognitive status (Mini Mental Status Examination) score), APOE genotype, or the presence of white matter hyperplasia showed no significant association

Interestingly, adiponectin 2 was lower in patients with rapid disease course compared with patients with non-rapidly progressive Alzheimer's disease (P = 0.
013)
.

The significance of this study lies in the discovery that plasma adiponectin-2 has the potential to be a diagnostic biomarker for Alzheimer's disease and does not appear to be related to currently used biomarkers
.

Plasma adiponectin-2 has the potential to be a diagnostic biomarker for Alzheimer's disease

Original source:
[Hermann P, Villar-Piqué A, Schmitz M, et al.

Plasma Lipocalin 2 in Alzheimer's disease: potential utility in the differential diagnosis and relationship with other biomarkers.
Alz Res Therapy.
2022;14(1):9.

Plasma Lipocalin 2 in Alzheimer's disease: potential utility in the differential diagnosis and relationship with other biomarkers.

 

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