Alzheimer's Disease

The current estimate is that there are more than 55 million people living with dementia worldwide, a figure that is expected to rise to 139 million by 2050. Every 3 seconds a new person develops dementia. The global cost of dementia is estimated to reach $2.8 trillion by 2030, according to the World Alzheimer Report 2024.

Alzheimer’s Disease International World Alzheimer Report 2024. Global changes in attitudes to dementia, September 2024

Alzheimer’s Disease (AD) is the leading cause of dementia in people over 65 years of age (more than 70% of cases).

AD is a neurodegenerative disease with an insidious and irreversible course that ends with the death of the patient, on average about 10 years after diagnosis. The risk of developing the disease doubles approximately every 5 years after the age of 65, affecting more than 30% of people over the age of 90.

Currently available treatments temporarily alleviate some of the symptoms but fail to modify the course of the disease, which makes the patient completely dependent for activities of daily living, causing a heavy emotional burden for caregivers and an enormous social and economic cost for families and social-health care systems.

It is now known that the pathological processes leading to AD, in particular the accumulation of amyloid peptides in the cerebral cortex, can start up to 20 years or more before the onset of the first symptoms of dementia. For this reason, most research into new treatments for AD aims to eliminate or prevent the formation of these clusters before the most disabling symptoms of the disease appear.

However, detecting those people (approximately 30% of those over 65) in whom the disease has already started, but who do not yet show symptoms in the general population, is not a simple task.

Robust biomarkers based on neuroimaging or cerebrospinal fluid (CSF) analysis capable of detecting the accumulation of Aβ peptides in the brain already exist. However, the high cost and/or complexity of using these procedures greatly limits their widespread use.

These limitations have exerted a strong stimulus for the development of more accessible biomarkers, based on blood tests of different molecules, in particular β-amyloid peptides, which could help in the early diagnosis of the disease.

Since its foundation in 2004, Araclon Biotech has contributed to this effort by developing ABtest-IA ELISA assays, fully validated analytically, whose main feature is that they allow accurate and robust determination of free (FP40 and FP42) and total (TP40 and TP42) levels of Aβ40 and Aβ42 in plasma.

We have recently developed a state-of-the-art assay that allows the simultaneous determination of total Aβ40 and Aβ42 levels in plasma by liquid chromatography coupled to mass spectrometry (ABtest-MS).

In studies carried out in different cohorts, the TP42/40 ratio has made it possible to discriminate patients with cortical beta-amyloid (Aβ) pathology confirmed by positron emission tomography (Aβ-PET positive) from those who are Aβ-PET negative with sensitivities between 77-89% and negative predictive value (NPV) between 64-97% which are highly relevant values for a screening test.

Examples:

AIBL
AB255
FACEHBI

Plasma TP42/40 ratio levels correlated significantly with Aβ-PET levels measured in in Standardized Uptake Value Ratio (SUVR) and Aβ42.

Additionally, the lower the TP42/40 ratio, the faster the Aβ-PET-SUVR increases and the higher the risk of developing dementia in patients with mild cognitive impairment (MCI).

Results of the Aβ-PET levels
Results of the Aβ42 levels
Results of the Aβ-PET-SUVR study
Results of the study in patients with mild cognitive impairment (MCI)

Valores menores de la ratio TP42/40 han sido encontrados asociados a un incremento cortical de Tau en regiones relacionadas con AD tras análisis de escáneres con [18F] flortaucipir.

Recientemente, hemos encontrado un paralelismo entre la trayectoria natural de la ratio TP42/40 en plasma y Aβ-PET-SUVR cortical. Estos hallazgos muestran una estrecha asociación entre los cambios en el plasma y el amiloide-β cerebral y apoyarían el uso futuro de la ratio TP42/40 en plasma como un marcador subrogado de la carga de Aβ cortical.

Results of the study with lower values of the TP42/40 ratio
Results of the study with TP42/40 in plasma and cortical Aβ-PET-SUVR

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