Alzheimer Dementia: Plasma P-tau181-Aβ42 ratio, which can efficiently screen for Alzheimer's disease

The neuropathological features of Alzheimer’s disease (AD) include the deposition of extracellular amyloid plaques composed of highly aggregated 40 to 42 amino acid amyloid β peptides (Aβ40 and Aβ42), and paired hyperphosphorylation Intracellular neurofibrillary tangles (NFTs) composed of tau protein spiral filaments.

According to reports, vascular dementia (VaD) is the second most common form of dementia in the elderly population after AD .
In VaD, there is a temporal relationship between the existence of cerebrovascular disease (CeVD) as evidenced by structural magnetic resonance imaging (MRI) results and the occurrence of cognitive impairment.
It is worth noting that CeVD MRI markers are often observed in the AD brain.
The existence of vascular disease and the related destruction of the blood-brain barrier may interact with the pathophysiological process of AD in an additive or synergistic manner, aggravating the decline of cognitive function.
It is worth noting that in certain geographical areas, such as Asia, the incidence of AD and CeVD may be higher, which may have an impact on prevention and treatment strategies.
10 Although the current imaging (Aβ-PET) and cerebrospinal fluid (CSF) ; Aβ42 or Aβ42/Aβ40 ratio) biomarkers show high diagnostic performance, but obstacles to clinical implementation still exist, including high cost, limited accessibility of PET scanners and loop scanners, and the traumatic nature of detection methods .
In response to this unmet clinical needs, focusing on the work was to evaluate the blood as an alternative source viable biomarkers, recently used the immune precipitation - mass spectroscopy, single molecule array (Simoa) immunoassay and other highly sensitive platforms do not With prospects.

A number of studies have found that plasma P-tau181 is closely related to PET Aβ load, and can distinguish AD from non-AD neurodegenerative diseases.
On the contrary, the decrease in the ratio of plasma Aβ42 and Aβ42/Aβ40 was related to changes in PET Aβ, while the total tau measurement value increased slightly in AD in some studies, but not in other studies.
However, most of the above-mentioned biomarker studies were conducted in white populations in North America and Europe, and the burden of AD was relatively "pure".
Whether the hypothetical clinical utility of these blood biomarkers can be applied to non-white cohorts with significant baseline CeVD is still unclear.In this way, Joyce R.
Chong and others of the National University of Singapore, based on Singapore’s non-cognitive impairment (NCI; n = 43), cognitive impairment without dementia (CIND; n = 91), AD (n = 44) and Subjects with vascular dementia (VaD; n = 22).
Using the single molecule array (Simoa), the correlation between plasma P-tau181, total tau, amyloid β (Aβ) 40 and Aβ42 and the corresponding ratios and neuroimaging methods were explored.

Vascular preventive diagnosis and immunity

They found that the P-tau181/Aβ42 ratio to Aβ+ (AUC=0.

889) and the area under the curve (AUC=0.
903) distinguishing AD Aβ+ and VaD Aβ- subjects were the highest.

In addition, the ratio of P-tau181/Aβ42 is related to hippocampal atrophy.

These biomarkers are not related to CeVD.

The important significance of this study is that the plasma P-tau181/Aβ42 ratio is non-invasive and can be used to identify AD patients with elevated brain amyloid in people with CeVD.

Original source: ncbi.

nlm.
nih.

ncbi.
nlm.
nih.
gov/33792168/" target="_blank" rel="noopener">Chong JR, Ashton NJ, et.
al.
, Chen CP.
Plasma P-tau181 to Aβ42 ratio is associated with brain amyloid burden and hippocampal atrophy in an Asian cohort of Alzheimer's disease patients with concomitant cerebrovascular disease.
Alzheimers Dement.
2021 Mar 31.
doi: 10.
1002/alz.
12332.
Epub ahead of print.
PMID: 33792168.
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