The aging of the population worldwide strongly correlates with the rising number of the cognitive impairments, which account for appr. 15% of the global burden of disease (WHO, 2001). Around 25% of the population above age 65 suffer from dementia, among which Alzheimer plays a leading role.  The global Alzheimer's epidemic currently affects 50 million people. It is estimated that ca. 150 million people will develop dementia by the year 2050. This will put an immense financial stress on the social system of appr. US$ 1.1 billion annually. Up till now there is no eligible strategy to cope with the global Alzheimer's epidemic.

Most sources of literature implicate that cognitive impairments strongly correlate with the neurodegenerative and cerebrovascular pathologies (Corriveau RA et al., 2016) with Alzheimer disease being the most prevalent example (appr. 65 % of cases). This knowledge lead to the development of several prevention strategies. The results of the long-term population studies clearly show that improvement in blood pressure control and vascular health reduces the age-specific incidence of dementia (Satizabal CL et. al, 2016).

The presence of C-terminal amidating activity, the reaction exclusively catalyzed by peptidylglycine α-amidating monooxygenase (PAM), in human cerebrospinal fluid (CSF) and in tissues of human central nervous system was demonstrated decades ago (Wand et al. 1985). The link between PAM activities and the emergence of the Alzheimer´s disease (AD) has been observed. One such example, is the continuous decrease of PAM activity in the CSF in AD patients within first 2 years after diagnosis and first lumbal puncture (Wand et al. 1987).

 

PAM is the only known enzyme to catalyze the formation of c‑terminally amidated bioactive peptide hormones and is a potential biomarker for early diagnosis of Alzheimer disease.

 

To a certain extent the onset and development of Alzheimer disease has been linked to the neurotoxic blood-derived components, which can end up in the cerebral interstitial fluid thought the leaky blood brain barrier (BBB). In fact, more than 80% of the AD patients show severe vascular damage, while the changes in vascular-health markers are already present in preclinical AD anamneses. Several peptide hormones amidated by PAM were shown to be reduced in patients with prevalent and incident AD (Nagata et al. 2019). Furthermore, the increased blood flow in brain and spinal cord was directly correlated with amount of the amidated peptides, which could exercise the protective or reparative mechanisms on the BBB integrity (Nagata et al. 2019)

 

The normalized balance of the amidated peptide hormone could restore the blood-brain barrier integrity and provide a powerful approach for the Alzheimer therapy.

 

Furthermore, the increased blood flow in brain and spinal cord was directly correlated with the amount of the amidated peptides, which could execise the protective or reparative mechanisms on the BBB integrity (Nagata et al. 2019). These findings indicate, that PAM together with its substrates represent powerful blood-based biomarkers for Alzheimer´s prediction.