Ludovica Caputo

Increased plasma levels of interleukin-1, interleukin-6 and α-1-antichymotrypsin in patients with Alzheimer's disease: peripheral inflammation or signals from the brain?

Plasma concentrations of interleukin-1beta (IL-1beta), interleukin-6 (IL-6), C reactive protein (CRP) and alpha-1-antichymotrypsin (ACT) in 145 patients with probable Alzheimers disease (AD) and 51 non-demented controls were measured. To investigate the cellular activation of peripheral immune system, plasma levels of neopterin were also investigated. Plasma levels of IL-1 were detectable in 17 patients with AD (13%) and only in one control (2%) and average levels of IL-1 were higher in AD patients than in controls (p < 0.001). IL-6 plasma levels were detectable in a higher proportion of AD and controls (53% and 27%, respectively), and were increased in patients with AD (p < 0.001). Plasma levels of ACT were increased in patients with AD (p < 0.001) and CRP levels were in the normal range. Plasma levels of neopterin were slightly lower in AD patients than in controls, but differences were not statistically significant. No significant correlation was observed between IL-1 and IL-6 levels or neopterin and cytokine levels in plasma from AD patients. Plasma levels of ACT negatively correlated with cognitive performances, as assessed by the mini mental state examination (MMSE; R = -0.26, p < 0.02) and positively correlated with the global deterioration state (GDS) of AD patients (R = 0.30, p < 0.007). Present findings suggested that detectable levels of circulating cytokines and increased ACT might not be derived by activation of peripheral immune system of AD patients. Detection of these molecules might be used for monitoring the progression of brain inflammation associated with AD.

The Hemochromatosis Gene affects the Age of Onset of sporadic Alzheimer's Disease.

In the present study we analysed the genotype of HFE, the gene involved in hemochromatosis, in 107 patients with sporadic late-onset AD and in 99 age-matched non-demented controls. We observed that patients carrying the mutant HFE-H63D allele had a mean age at onset of 71.7 +/- 6.0 years versus 76.6 +/- 5.8 years of those who were homozygous for the wild-type allele (p = 0.001). The frequency of the HFE-H63D mutation was highest (0.22) in the patients aged <70 years at the time of disease onset, whereas it was 0.12 in those with disease onset at an age of 70-80 years, and 0.04 in those aged more than 80 years. The APOE genotype did not significantly modify the effect of HFE on age at onset. We conclude that mild disturbances of iron homeostasis associated with a common genetic determinant may interact with other pathogenic mechanisms involved in AD. HFE mutations may anticipate AD clinical presentation in susceptible individuals.

The apolipoprotein E epsilon4 allele and the response to tacrine therapy in Alzheimer's disease.

The objective of our study was to evaluate the effects of the apolipoprotein E (ApoE) phenotype and gender on the response to tacrine treatment in Alzheimer’s disease (AD). ApoE phenotyping was performed on 76 patients treated with tacrine for AD. This group comprised 33 ApoE ε4 allele carriers (ε4+) and 43 non‐ε4 carriers (ε4–). Patients were treated blindly in relation to the ApoE phenotype, with incremental tacrine dosages ranging from 40 mg/day up to the highest dosage (160 mg) tolerated without side‐effects. At least 6 weeks elapsed between each increase. Changes in the scores for the Alzheimer Disease Assessment Scale‐Cognitive Component (ADAS‐Cog) between baseline and each increment in dosage were assessed in the ε4– and ε4+ groups. The cut‐off point for being considered as responsive to tacrine treatment was a 4‐point decrease in the ADAS‐Cog score.

Association of the Apolipoprotein E ε4 Allele with Late-Onset Depression

Apolipoprotein E (ApoE) phenotyping was determined in 42 subjects with Alzheimer’s disease (AD), 49 with depression, including 26 with early-onset depression (EOD) and 23 with late-onset depression (LOD), and 49 controls. In the EOD group, the frequency of the ApoE Ε4 allele was not different from the control frequency (p = 0.532) but was significantly lower than in AD (p < 0.001). In the LOD group, the ApoE Ε4 frequency was significantly higher than in the controls (p = 0.034) but was not different from that in the AD group (p = 0.229). Individuals with ApoE Ε4 were at greater risk of getting AD (odds ratio, OR = 5.5, 95% confidence interval, CI, 2.0–14.0) or LOD (OR = 6.1, 95% CI, 1.9–19.0) than of EOD (OR = 0.7, 95% CI, 0.2–2.5). These results suggest an association between the ApoE Ε4 allele frequency and LOD. Patients with LOD could be at risk of developing AD by an Ε4-dependent pathway.

Apolipoprotein E phenotypes in demented and cognitively impaired patients with and without cerebrovascular disease

Controversy exists regarding the apolipoprotein E (ApoE) ɛ4 allele association with vascular dementia (VaD), ranging from increased ɛ4 frequency, similar to that found for Alzheimers disease (AD), to no association between the ɛ4 allele and VaD. To clarify further the relationship between ApoE alleles polymorphism and cerebrovascular disease (CVD) in demented and cognitively impaired patients, we examined the ApoE phenotypes in a sample of 280 patients: 155 with AD, 21 with VaD, 32 with mixed dementia (MD), 45 with mild cognitive impairment (MCI) but without CVD, and 27 in which vascular disease was the most probable cause of cognitive decline [vascular mild cognitive impairment (VMCI)]. Our results show that the frequency of the ApoE ɛ4 allele in patients over 70 years old with clinically diagnosed VaD and VMCI does not differ significantly from that of controls. In contrast, ApoE ɛ4 allele‐bearing individuals had greater risk of having late‐onset AD (OR=8.8; 95% Cl 3.7–21.0), or non‐vascular cognitive impairment (OR=7.0; 95% Cl 2.5–19.0).

Alpha-1-antichymotrypsin and oxidative stress in the peripheral blood from patients with probable Alzheimer disease: a short-term longitudinal study

To evaluate the stability and reproducibility of selected peripheral oxidative stress markers and their possible relation to cognitive performance, three different blood samples were taken at 7- to 10-day intervals from 11 patients with probable Alzheimer disease (AD) and 11 nondemented controls. Blood samples were also collected once from 6 patients with vascular dementia (VD). Alpha-1-antichymotrypsin (ACT), C-reactive protein (CRP), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), lactoferrin (LTF), and total lipid peroxidation (LPO) were then measured. Blood levels of ACT and GSH-Px were increased in AD patients but not in patients with VD. Levels of LTF, CRP, and LPO were comparable between AD patients and controls. Erythrocyte SOD activity was increased in AD patients. Blood levels of ACT negatively correlated with LPO levels and positively correlated with scores of the Global Deterioration Scale of AD patients. ACT might be implicated in controlling oxidative damage of blood lipids and their turnover during the progression of AD.

Apolipoprotein E genotype in senile dementia and Down's syndrome

Apolipoprotein E genotypes were determined in 30 healthy elderly controls, 42 patients with Alzheimers disease, 13 subjects with vascular dementia and 31 individuals with Downs syndrome. The frequency of epsilon4 allele carriers was significantly increased in the Alzheimers disease group (chi(2)=4.918, P<0.05) but also in the vascular dementia subjects (P<0.01, Fishers exact test). The established relationship between genotype and age at onset of Alzheimers disease was not statistically significant in these data. Frequencies of the genotypes in the Downs syndrome group did not differ from those of controls. The results obtained in this sample of the Italian population suggest that the apolipoprotein E genotype may be of limited use in the differential diagnosis of dementia.

Reversible Parkinson's Dementia Associated with Withdrawal of Androgen‐Deprivation Therapy for Prostate Cancer

To the Editor: An 80-year-old man presented because of an approximately 10-month history of increasingly slow gait, leg stiffness with nocturnal cramps, and very fine hand tremor, associated with depression. A single visual hallucination, mild apathy, rapid eye movement sleep behavior disorders, and subtle cognitive impairment were reported. His past medical history included prostate carcinoma in 1996 (Gleason score 3–4; prostate-specific antigen 12 ng/mL), treated using radical radiotherapy, and subsequent long-term androgen-deprivation therapy (ADT) with cyproterone acetate (100 mg/d) and intramuscular injections of triptorelin (3.75 mg/month). His family history was positive for Parkinson’s disease (PD) and late-onset dementia. Neurological examination (March 2013) showed mild extrapyramidal syndrome with bradykinesia, increased upper limb tone (left>right), decreased left arm swing, mild camptocormia, very mild rest and postural tremor, and reduced eye blinking. A diagnosis of PD was

Contents Vol. 20, 2001

M.Z. Al Kawi, Riyadh A. Alpérovitch, Paris D.W. Anderson, Bethesda, Md. E. Beghi, Milano M.M. Ben Hamida, Tunis F. Bermejo, Madrid N.E. Bharucha, Bombay G. Boysen, Copenhagen M.M.B. Breteler, Rotterdam R. D’Alessandro, Bologna J.F. Dartigues, Bordeaux G.M. Franklin, Seattle, Wash. G. Friday, Wynnewood, Pa. R. Hart, San Antonio, Tex. W.A. Hauser, New York, N.Y. C. Ketzoian, Montevideo S.J. Kittner, Baltimore, Md. W.C. Koller, Miami, Fla. A. Korczyn, Tel Aviv J.F. Kurtzke, Washington, D.C. S.-M. Lai, Kansas City, Kans. J. Matias-Guiu, Alicante R.P. Mayeux, New York, N.Y. K. Nakashima, Yonago K. Nelson, Bethesda, Md. L. Nelson, Stanford, Calif. A.H. Rajput, Saskatoon D. Rosselli, Bogotá D. Royall, San Antonio, Tex. R.L. Sacco, New York, N.Y. I. Skoog, Göteborg C. Tanner, Sunnyvale, Calif. X. Zhang, Beijing Editor-in-Chief

Apolipoprotein E Genotype in Vascular Dementia

The e4 allele of apolipoprotein E (ApoE) has been associated with Alzheimer’s disease (AD): the frequency of the e4 allele is elevated in samples of AD patients1,2 and individuals with a single or double dose of the s4 allele have earlier onset of AD symptoms1. Furthermore, subjects with one or two e4 alleles have been shown to have increased amounts of the neurofibrillary tangles and amyloid plaques associated with AD3.