Oxidative imbalance in different neurodegenerative diseases with memory impairment.
BACKGROUND
Byproducts of oxidative metabolic reactions could play a role in the pathogenesis of several neurodegenerative diseases (ND) including Alzheimer's disease (AD). We designed a study aimed at investigating a large set of oxidative and antioxidant markers in a sample of patients affected by different forms of dementia or memory impairment.


METHODS
Serum levels of coenzyme Q(10), malondialdehyde (MDA), the total, oxidized and reduced forms of glutathione (GStot, GSSG and GSH, respectively), reactive oxygen species, anti-oxidized low-density lipoprotein antibodies and antioxidant power (PAO) were investigated in patients affected by AD, mild cognitive impairment, dementia with Lewy bodies and Parkinson's disease with dementia. The patient sample (n = 66) was compared with healthy subjects (HC; n = 62), and a comparison across pathological subgroups was also performed. A multivariate logistic regression model was implemented in order to calculate an algorithm model for predicting the risk of developing a neurodegenerative disorder.


RESULTS
The comparison between the memory deficit (MD) group and HC showed a significant difference for MDA (MD: 6.3 ± 2.8 μg/l; HC: 9.1 ± 4.9 μg/l; p = 1.7 × 10(-6)), GStot (MD: 260.4 ± 62.6 mg/l; HC: 306.5 ± 60.7 mg/l; p = 2.2 × 10(-5)), GSH (MD: 208.9 ± 68.4 mg/l; HC: 295.3 ± 101.3 mg/l; p = 2.2 × 10(-7)) and PAO (MD: 1,066.5 ± 247.7 μmol; HC: 954.9 ± 200.4 μmol; p = 0.8 × 10(-3)). By contrast, no differences in the levels of the studied markers were detected across the different forms of ND. An older age, higher levels of PAO, lower levels of GSH and MDA and the use of cardiovascular or antidepressant drugs were the most important factors associated with the carrier ship of neurodegenerative disorder.


CONCLUSIONS
To our knowledge, this is the first study reporting similar oxidative imbalance in different forms of memory impairment, regardless of the specific etiology. Low GSH levels could be considered as a favorable factor in ND; at the same time it could be suggested that higher levels of PAO represent a counteracting mechanism against an increased oxidative stress. The association between vascular risk factors, depressive status and cognitive impairment is in line with findings in the literature.
Gironi
M
M
Don Carlo Gnocchi Foundation, Santa Maria Nascente Clinical Research Center, Milan, Italy. mgironi @ dongnocchi.it
Bianchi
A
A
Russo
A
A
Alberoni
M
M
Ceresa
L
L
Angelini
A
A
Cursano
C
C
Mariani
E
E
Nemni
R
R
Kullmann
C
C
Farina
E
E
Martinelli Boneschi
F
F
D000368:Aged; D000369:Aged, 80 and over; D000906:Antibodies / Q000097:blood; D016022:Case-Control Studies; D003072:Cognition Disorders / Q000097:blood / Q000503:physiopathology*; D005260:Female; D005978:Glutathione / Q000097:blood; D006801:Humans; D008077:Lipoproteins, LDL / Q000276:immunology; D016015:Logistic Models; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008569:Memory Disorders / Q000097:blood / Q000503:physiopathology*; D019636:Neurodegenerative Diseases / Q000097:blood / Q000503:physiopathology*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology*; D010865:Pilot Projects; D017382:Reactive Oxygen Species / Q000097:blood; D014451:Ubiquinone / Q000031:analogs & derivatives / Q000097:blood
D000906:Antibodies; D008077:Lipoproteins, LDL; D017382:Reactive Oxygen Species; C099252:oxidized low density lipoprotein; D014451:Ubiquinone; D008315:Malondialdehyde; C024989:coenzyme Q10; D005978:Glutathione