Heavy Metals and Essential Metals Are Associated with

Overview

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Key numbers

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patients (4–6). Here, in the first place, we mean metals that are present in the body under
Int. J. Mol. Sci. 2023, 24, 467 Fe (Figure 4), S, K, Se, Co, Mn, Ni, Na, Mg, Tl, and Li (Table 1). 3 of 28
in Table 1. Macro‐ and microelements that correlated with the high number of CSF AD
Fe (Figure 4), S, K, Se, Co, Mn, Ni, Na, Mg, Tl, and Li (Table 1).
in Table 1. Macro- and microelements that correlated with the high number of CSF AD
Fe (Figure 4), S, K, Se, Co, Mn, Ni, Na, Mg, Tl, and Li (Table 1).
Table 1. Correlations of CSF AD biomarkers with macro- and microelements.
eters that were classified into 6 groups (factors) after analysis (Table 2). Factors explained
73.2% of the total variance in analyzed CSF macro- and microelements (with Bartlett’s
were classified into six groups (factors) after analysis (Table 3). Factors explained 66.1%
Table 2. CSF macro- and microelements and their factor loadings for 6 groups (factors) (given by
Table 3. Plasma macro- and microelements and their factor loadings for 6 groups (factors) (given by
analysis of CSF macro- and microelements with CSF AD biomarkers are given in Table 4
in Table 5 and Figure 7. The most interesting finding is that following PCA heavy metals
Table 4. Results of linear regression analysis; comparison of factors obtained by PCA of CSF macro-
95% confidence intervals are given by linear regression analysis (statistically significant factors are
Table 5. Results of linear regression analysis; comparison of factors obtained by PCA of plasma
and 95% confidence intervals are given by linear regression analysis
ment groups revealed by the PCA. Effect sizes and 95% confidence intervals are given by linear
significant 95% confidence intervals
microelements measured in CSF (Table 6), and plasma (Table 7), as well as an association
plasma (Table 7). Information on age, Mini‐Mental State Examination (MMSE), and APOE
microelements measured in CSF (Table 6), and plasma (Table 7), as well as an association
plasma (Table 7). Information on age, Mini-Mental State Examination (MMSE), and APOE
were extracted (Table 6, Table 7). When analyzing the association of CSF AD biomarkers
Table 6. Most significant redescriptions given by the combination of CSF AD biomarkers (first view—W1) and macro- and microelements measured in CSF (second
Redescription Specific for: HC (%) MCI (%) AD (%) W1R W2R JS p-Value
Redescription Specific for: HC (%) MCI (%) AD (%) W1R W2R JS p-Value
Redescription Specific for: HC (%) MCI (%) AD (%) W1R W2R JS p-Value
Redescription Specific for: HC (%) MCI (%) AD (%) W1R W2R JS p-Value
Data are presented as percentages of diagnoses and ranges of CSF biomarkers and elements. W1R refers to the first redescription query (constructed using attributes from the first
Table 7. Most significant redescriptions given by the combination of CSF AD biomarkers (first view—W1) with macro- and microelements measured in plasma
Redescription Specific for: HC (%) MCI (%) AD (%) W1R W2R JS p-Value
AD 0% 8.6% 30.1% Age (49–82) Li in plasma (15–48) 0.64583 2.475 × 10−8 *
AD 0% 5.7% 32.3% MMSE (5–28) Li in plasma (15–32) 0.51613 4.924 × 10−6 *
Redescription Specific for: HC (%) MCI (%) AD (%) W1R W2R JS p-Value
AD 6.6% 22.9% 45.2% T-tau (313.77–2259) Ca in plasma (73.6–90.4) 0.54839 0.001 *
AD&MCI 6.6% 45.7% 45.2% Age (49–83) Pb in plasma (103.9–223.7) 0.56731 0.006 *
AD&MCI 0% 22.8% 41.9% Age (49–82) Mn in plasma (0.83–2.35) 0.63514 4.880 × 10−6 *
AD&MCI 6.6% 48% 43% Age (49–83) Co in plasma (0.26–1.07) 0.55769 0.007 *
Redescription Specific for: HC (%) MCI (%) AD (%) W1R W2R JS p-Value
AD&MCI 6.6% 31.4% 46.2% p-tau181 (21.6–319.16) Mo in plasma (0.72–12.02) 0.55556 0.003 *

Methods (brief)

10 Nash Family Department of Neuroscience, Friedman Brain Institute, Ronald M. Loeb Center for
spectroscopy (ICP-MS) to determine macro- and microelements in CSF and plasma, and enzyme-
4.1. Participants and Sample Collection
MCI (88,89), and 19 were HC. CSF samples were collected from all participants by lumbar
2000× g for 10 min, CSF samples were aliquoted in polypropylene tubes and stored at
−80 ◦ C. Venous blood samples were collected from 143 participants in the morning on an
empty stomach. Samples were collected using plastic syringes (with 1 mL of acid citrate
dextrose as an anticoagulant). Thrombocyte-free plasma was collected by centrifugation,
first at 1100× g for 3 min and then at 5087 g for 15 min. Plasma samples were stored
Inductively coupled plasma mass spectroscopy (ICP-MS) was used for the measure-
the samples with Cr from the needles used for sample collection, it was excluded from
statistical analysis. ICP-MS was performed on Agilent 7500cx (Agilent Technologies, Tokyo,
Japan). Before the analysis, CSF samples were diluted at 1:10, while plasma samples were
Shield Plate system and Ni sampler and skimmer cones. Daily optimization of ICP-MS
HEPA filters were used for sample preparation and analysis. Quantification of elements
concentration in samples was done by the standard addition method (matrix-matched
test items and sample size for factor analysis was assessed by Bartlett’s χ2 test of sphericity
enzyme-linked immunosorbent assay; Fe, iron; HC, healthy controls; Hg, mercury; ICP-MS,

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Update history

The five most recent substantive edits to this page, classified major (evidence or structure moved), correction (a published value or statement was wrong and has been fixed), or minor (narrative rewritten without changing the underlying evidence). Each description is derived from what the edit did to this page; the linked commit is the authoritative record, routine regeneration passes are excluded, and the full version history lives in git. When DOI minting comes online (see schema docs), each entry below will also link to a version-pinned DataCite DOI.

Commit	Date	Change	Description
b01ec52c	2026-08-04	major	2 sections added
d49e450f	2026-08-03	major	5 sections added; narrative text revised