Abstract

Aim: In this review paper we propose a method to make an early diagnosis of the Alzheimer’s Disease (AD), the most common form of neurodegenerative dementia. Background: Glymphatic System (GS) is the main means of eliminating waste substances in the central nervous system (CNS); if it does not work properly, waste substances accumulate in CNS until to cause AD. Basal Forebrain is the most important component of a much broader system of cholinergic cells distributed throughout the Central Nervous System (CNS). This structure regulates attention, learning and memory and its destruction is considered responsible for the cognitive AD alterations. The characteristics of AD patients, that interest us most, are the lack of Acetylcholine, and the Orexin excess; we think that the hypothalamus produces more Orexin to stimulate cholinergic cells, indispensable for a correct CNS functioning. We want to identify these patients by detecting the Orexin excess. Early Diagnosis Model. Of course we could take a cerebrospinal fluid sample and dose Orexin but this method is risky and painful for the patient’s health, therefore unsuitable for large numbers of patients. We propose a fairly simple method for the early diagnosis of AD: if we temporarily eliminate the Orexin excess, with Dual Orexin Receptor Antagonist (DORA), i.e. Suvorexant, we can intercept the Orexin increase and demonstrate the decrease in Acetylcholine with a Functional Magnetic Resonance or a Polysomnography, many years before the AD symptoms occur.

Highlights

  • Glymphatic System (GS) is the main means of eliminating waste substances in the central nervous system (CNS); if it does not work properly, waste substances accumulate in CNS until to cause Alzheimer’s Disease (AD)

  • Basal Forebrain is the most important component of a much broader system of cholinergic cells distributed throughout the Central Nervous System (CNS)

  • We propose a fairly simple method for the early diagnosis of AD: if we temporarily eliminate the Orexin excess, with Dual Orexin Receptor Antagonist (DORA), i.e. Suvorexant, we can intercept the Orexin increase and demonstrate the decrease in Acetylcholine with a Functional Magnetic Resonance or a Polysomnography, many years before the AD symptoms occur

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Summary

Background

Alzheimer’s Disease (AD) is the most common form of degenerative dementia [1], characterized by widespread neuron destruction, a sharp decrease in Ace-. We know that the genetic mutations responsible for the genetic forms of AD often interfere with the correct function of the main cleaning mean of our Central Nervous System(CNS), and the Glimphatic System (GS) [2] [3] [4]. We think that this happens in the sporadic forms of AD, for other reasons, which often involve the breaking of the Blood-Brain-Barrier integrity, above all, aging [5]

The CNS Clearance and the Glymphatic System
Intracellular Clearance Mechanisms
Extracellular Clearance Mechanism
Neurotransmitters
Basal Forebrain Cholinergic System
Orexin
Conclusion
Findings
Conflicts of Interest
Full Text
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