Alzheimer's disease and disseminated mycoses.

Alzheimer's disease (AD) is characterized by the presence in the brain of amyloid plaques and neurofibrillary tangles that provoke neuronal cell death, vascular dysfunction and inflammatory processes. In the present work, we have analyzed the existence of fungal infection in AD patients. A number of tests have been carried out in blood serum, including the detection of antibodies against several yeast species and fungal proteins, and also the presence of fungal (1,3)-ß-glucan. Results from this analysis indicate that there is disseminated fungal infection in the majority of AD patients tested. Of interest, several AD patients contain high levels of fungal polysaccharides in peripheral blood, reflecting that disseminated fungal infection occurs in these patients. Together, these results suggest the presence of disseminated mycoses in blood serum from AD patients. To our knowledge these findings represent the first evidence that fungal infection is detectable in blood samples in AD patients. The possibility that this may represent a risk factor or may contribute to the etiological cause of AD is discussed.

Fungal infection in cerebrospinal fluid from some patients with multiple sclerosis.

Multiple sclerosis (MS) is the prototypical inflammatory disease of the central nervous system and spinal cord, leading to axonal demyelination of neurons. Recently, we have found a correlation between fungal infection and MS in peripheral blood of patients. The present work provides evidence of fungal infection in the cerebrospinal fluid (CSF) of some MS patients. Thus, fungal antigens can be demonstrated in CSF, as well as antibodies reacting against several Candida species. Comparison was made between CSF and blood serum for the presence of fungal antigens (proteins) and antibodies against different Candida spp. Analyses of both CSF and serum are complementary and serve to better evaluate for the presence of disseminated fungal infection. In addition, PCR analyses indicate the presence of DNA from different fungal species in CSF, depending on the patient analyzed. Overall, these findings support the notion that fungal infection can be demonstrated in CSF from some MS patients. This may constitute a risk factor in this disease and could also help in understanding the pathogenesis of MS.

Fungal infection in a patient with multiple sclerosis.

Multiple sclerosis (MS) is a chronic, inflammatory disease of the central nervous system, whose causes are still unknown. We have proposed that MS, as well as some ophthalmologic diseases, are associated with fungal infection. In the present study, we closely monitored a patient with MS over a three-year period. Antibodies against different Candida spp. were detected in peripheral blood serum, although the titer of these antibodies fluctuated. The presence of fungal macromolecules, such as proteins, polysaccharides, and DNA, was also tested. In several sera samples, antigens related to C. famata were evidenced by the slot-blot test using a rabbit polyclonal antibody against these species, while high levels of ß-1,3 glucan were detected with the commercial Fungitell assay. Despite the variations by sample, we concluded that all fungal macromolecules, that is, proteins, polysaccharides, and DNA, were present in blood from the MS patient which was analyzed. Several fungal species were identified using polymerase chain reaction (PCR) followed by sequencing. Antibodies against Candida spp. as well as C. famata-related antigens were also detected in cerebrospinal fluid (CSF). Our findings provide support for the notion that disseminated mycosis is present in this patient.

Association between multiple sclerosis and Candida species: evidence from a case-control study.

Candida infection among multiple sclerosis (MS) patients has not been studied in depth. We determined whether there is an association between serological evidence of Candida infection and MS. Blood specimens were obtained from 80 MS patients and 240 matched controls. Immunofluorescence analysis and ELISA were used to detect Candida species antibodies and slot-blot to detect antigens. Using immunofluorescence analysis, moderate to high concentrations of serum antibodies to Candida famata were present in 30 (37.5%) MS patients vs. 30 (12.5%) controls (p < 0.001). Results for Candida albicans were 47.5% (38/80) in MS patients vs. 21.3% (51/240) in controls (p < 0.001), for Candida parapsilosis 37% (28/80) vs. 17.1% (41/240) (p < 0.001) and for Candida glabrata 46.3% (37/80) vs. 17.5% (42/240) (p < 0.001), respectively. After adjusting for age and gender, the odds ratios (95% confidence intervals) for MS, according to the presence of Candida antigens were: 2.8 (0.3-23.1, p = 0.337) for Candida famata; 1.5 (0.7-3.4, p = 0.290) for Candida albicans; 7.3 (3.2-16.6, p < 0.001) for Candida parapsilosis; and 3.0 (1.5-6.1, p = 0.002) for Candida glabrata. The results were similar after excluding ten patients on immunosuppressants. The results of this single study suggest that Candida species infection may be associated with increased odds of MS.

Histamine-N-methyl transferase polymorphism and risk for multiple sclerosis.

BACKGROUND: Histamine N-methyltransferase (HNMT) is the main metabolizing enzyme of histamine (a mediator of inflammation implicated in the pathogenesis of multiple sclerosis-MS) in the CNS. We have investigated the possible association between a single nucleotide polymorphism of the HNMT (chromosome 2q22.1), that causes the amino acid substitution Thr105Ile (decreasing enzyme activity) and the risk for MS. METHODS: We studied the frequency of the HNMT genotypes and allelic variants in 228 MS patients and 295 healthy controls using a PCR-RLFP method. RESULTS: The frequencies of the HNMT genotypes and allelic variants did not differ significantly between MS patients and controls, and were unrelated with the age of onset of MS, gender, and course of MS. CONCLUSION: The HNMT polymorphism is not related with the risk for MS.