Some Biochemical Markers in Patients with Alzheimer's Disease.

BACKGROUND: Metal ions effect on homeostasis of Alzheimer's disease (AD) patients. The aim of this study was to assess the metal ions (Iron, Zinc and Copper) and CBC in patients with AD in comparison with normal range.
METHODS: The samples of study were 17 patients with AD in Tehran's aging centers in 2015, selected as an access sample. Blood samples were analyzed in a pathobiology laboratory. Data were analyzed by one sample t-test.
RESULTS: According to the normal range, provided by laboratory, there is a significant difference between zinc in patients with AD and normal reference interval (α=0.01). The comparison of CBC of the AD patients with normal group showed also some decreases.
CONCLUSION: Zinc value in AD patients is significantly lower than normal range. It should be repeated by a larger sample size.

Introduction

Alzheimer’s disease (AD) is known as the most common form of dementia and degenerative disease (1). AD is related to the deposit of amyloid plaques and neurofibrillary tangles within the cortex. Several factors result in AD but there is no clear casual factor for AD. Most of studies assigned to genetic and biological structures.

As we know, the formation of signs and symptoms of AD are not only influenced by APOE and other genes, but also mediated by some environmental factors. Metals as mediated factors are studied in several studies.

The highlighted lesion in the brain of people with AD is the amyloid plaques that include Amyloid β (Aβ) peptides derived from Amyliod precursor protein (APP). Toxicity of Amiloid β is resulted from abnormal interaction with metals like zinc, copper and iron in Neocortex (2–4). Homeostasis of metals can be traced in the serum/plasma in AD patients. One study explained the effects of metals in AD (5). Copper, zinc and iron are elevated in AD-affected cortex, repeated in other studies (6, 7).

These metals are found in amyloid plaques and neurofibrillary tangles (8). They bind to the Aβ and deposit into the Aβ (9). Therefore, sequestration of these metals into senile plaques leads to the loss of cellular and synaptic metals. This synaptic loss is relevant to the maintenance of normal cognition.

ApoE isoforms bind to metals such as iron, zinc and copper (10). Some evidence focus on the effect of metals on expression levels of Apolipoproteins. The expression of Apo A and B has been regulated by zinc and copper (11). Altered metal rate in AD affect the expression of ApoE. Moreover, these metals play an important role in the regulation of the AD-related proteins (APP and tau) (12)

We do not know that the metal ions dyshomeostasis in AD is a cause or consequence of disease, the findings are controversial. There is an age-dependent decrease of serum zinc, approximately 0.4% per year (13). There is a direct relation between AD and metal ions, but other studies suggest that it is not significant (4).

The aim of this study was to assess the metal ions (Iron, Zinc and Copper) and CBC in patients with Alzheimer’s disease in comparison with normal range.

Methods

Among a group of patients with AD, 17 patients who signed the testimonial, blood sample were collected. Samples were analyzed for zinc, Iron, copper and CBC in a pathobiological laboratory. According to the existing reference interval, data were analyzed by one sample t-test.

- Iron in serum is analyzed by FreroZink method.

- Zinc in serum is analyzed by Photometric method.

- Copper in serum is analyzed by photometric method.

- CBC test was performed for all participants

Results

The results of CBC test showed a decrease for all participants; data are presented in Table 1 and Fig. 1.

Table 1:

Descriptive analysis of hematology test

	WBC	RBC	Hematoglobin	Hematocrit	M.C.W	M.C.H	M.C.H.C	R.D.W
Observed average	5.61	4.64	13.85	37.61	84.62	29.94	34.65	14.03
Normal verage	7.5	4.65	13.5	41.5	90	29.5	33	12.8
Ref. interval	4–11	3.8–5.5	12–15	36–47	80–100	27–32	31.5–34.5	11.6–14

Fig. 1:

Results of hematology

As it shows in Table 1, there was no significant deficit in CBC of the participants. Obtained data were categorized and descriptive analysis is presented in Table 2.

Table 2:

Descriptive analysis of data

	n	Observed Mean	Reference Interval	SD	Standard error mean
Iron	17	55.76	37–145	19.60	4.75
Zinc	17	64.35	80–120	13.50	3.27
Copper	17	119.29	80–155	23.12	5.60

As it shows in Table 2, each variable was analyzed and descriptive data (Mean, standard deviation and standard error mean) are provided for analysis. Results of one sample t-test are presented in Table 3. According to the degree of freedom (df), t is achieved from table distribution and then compared with obtained t. There was a significant difference between obtained data and distribution range.

Table 3:

Results of one-sample t-test

	t	df.	Mean difference	99% confidence
				Lower	Upper
Iron	11.72	16	55.76	41.87	69.65
Zinc	19.64	16	64.35	54.78	73.91
Copper	21.27	16	119.29	102.91	135.67

A reference interval was provided by laboratory as normal range for each variable. Iron, Zinc and Copper are 37–145, 80–120 and 80–155, subsequently. Therefore, according to the provided interval reference, only the Zinc shows a significant decrease.

Discussion

Zinc as a metal in the brain, has various functions. Zinc has numerous functions in AD. Zinc is essential in processing of the APP (13, 14) and in the enzymatic degradation of the Aβ peptide (15, 16).

Zinc has a role in sustaining the adhesiveness of APP during cell-cell and cell-matrix interactions (17). APP can be processed by the Amiloidogenic pathway or Non-Amiloidogenic pathways. Amiloidogenic pathway leads to the production of Aβ and in healthy brain; the non-Amiloid pathway is predominant APP processing pathway (18, 19). Zinc in patients with AD is lower than reference interval. Decrease in serum zinc is depended on aging and it decreases approximately 0.4% per year (15).

Overall, decrease of zinc is approved in most of studies but with different explanations. It needs to more accurate studies for presenting the relationship between zinc and AD.

Conclusion

Copper, zinc and iron show significant differences in AD patients and normal older adults. There is significant decrease in zinc serum of AD patients, but copper and iron did not show significant differences.

Ethical consideration

Ethical issues (Including plagiarism, informed consent, misconduct, data fabrication and/or falsification, double publication and/or submission, redundancy, etc.) have been completely observed by the authors.