Effects of taurine on metal cations, transthyretin and LRP-1 in a rat model of Alzheimer’s disease

Alzheimer's disease (AD), the most common type of dementia, is a neurodegenerative disease that ultimately leads to death, is characterized by advanced loss of cognitive functions and significantly reduces the quality of life [1]. During the progression of AD, amyloid beta (Aβ) monomers aggregate, polymerize and form neurotoxic oligomers that cause cognitive disorders [2]. There is impaired clearance of amyloid beta 1–42 (Aβ 1–42) in AD. Aβ 1–42 accumulating in the central nervous system is particularly responsible for the development of the disease [1].

Definitive criteria for diagnosis, treatment and prevention of AD, which is one of the biggest health problems especially for aged individuals today, have not been established. Many studies in the literature are aimed at determining these criteria. There is an increasing number of studies on the determination of a blood-based biomarker that can be measured minimal invasive methods. Plasma Aβ 1–42 levels, metal cation levels and transthyretin (TTR) levels are possible biomarkers for AD [3], [4], [5].

TTR, a transporter protein, is known especially for its role in the transport of thyroxine hormone and retinol [6]. TTR is also thought to be a transporter for Aβ 1–42. TTR binds to Aβ peptide and transports it to the periphery, thus prevents its toxicity [7]. In some studies in the literature, TTR levels decreased in serum and cerebrospinal fluid in Alzheimer's patients. This suggests that TTR can be used as a biomarker for AD [8], [9].

TTR transports amyloid beta from the brain to the periphery, not from the periphery to the brain. However, the details of this relocation are not known exactly. This unidirectional transport is thought to be mediated by the low density lipoprotein (LDL) related protein-1 (LRP-1) receptor, which is located only on the brain side of the blood brain barrier [10].

Transthyretin is also the amyloidogenic protein that accumulates primarily in the heart in cardiac transthyretin amyloidosis. The TTR form that accumulates in TTR-induced cardiac amyloidosis is the toxic monomer form. The form thought to act as a protective agent by transporting Aβ in AD is the first stable form, the tetramer form [11]. There is no curative treatment for TTR-induced cardiac amyloidosis like AD [12].

Metal cations and their imbalances can take part in progression of AD. It has been shown that Aβ senile amyloid plaques in brain contain high levels of iron (Fe), copper (Cu) and zinc (Zn) ions [13]. On the other hand, non-ceruloplasmin Cu was found to be high in Alzheimer's patients, as in Wilson's patients. In addition, it has been reported that urinary Cu excretion is higher in Alzheimer's patients compared to the control group [14]. It is thought that Alzheimer's patients cannot maintain especially their copper metabolic balance and are prone to copper imbalance [15]. Although the metal cation imbalance in AD is not completely clear, it has been reported that the copper imbalance in the aging human brain has a negative effect on both energy production function and antioxidant functions. In addition, the chemical aging process may be aggravated by the activation of oxidative stress. As a result, mitochondrial deficits, energy depletion in neurons and production of misfolded proteins may occur. Thus, metal cation imbalance may contribute to the pathogenesis of AD [16].

Taurine (2-aminoethane sulfonic acid) is known for its antioxidant and anti-apoptotic properties [17]. Chronic supplementation of taurine has been shown to significantly improve hippocampus-dependent cognitive impairment in experimental AD animal models [18], [19]. Also, the use of taurine with the combination of doxycycline in TTR-induced cardiac amyloidosis stopped the progression of cardiac amyloidosis and neuropathy. Taurine has shown a fibril-disrupting effect on the toxic monomer form of TTR [20], [21].

This study aimed at collecting information about the possible blood-based biomarkers and the mechanisms of Aβ 1–42 clearance in the AD model created by intracerebroventricular (icv) Aβ 1–42 injection. In addition, the relationship between brain and cardiac amyloidosis was investigated. It was aimed to investigate the possible metal cation imbalance in AD and to show its relationship with impaired amyloid clearance and its parameters. It was desired to examine the effects of taurine, known for its antioxidant properties, on metal cations and amyloid clearance parameters.

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