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Biomedical subjects

M Lehtovirta

Publications and source records attributed to M Lehtovirta.

At least 19 recordsLinked to original sources
PubMed2002

Auditory adaptation is differentially impaired in familial and sporadic Alzheimer's disease.

Neurophysiologic measures are particularly sensitive to alterations in attention and arousal. The purpose of this study was to evaluate the auditory adaptation of normal and mildly demented elderly people. We compared the automatic behavior of an auditory evoked potential (N100) in three age-matched groups of elderly subjects, one with familial Alzheimer's disease (AD), one with sporadic AD and one healthy group. All AD subjects corresponded clinically and neuropsychologically with the early stage of dementia. The dynamic range of auditory adaptation is known to be related to age, and normal auditory adaptation for the age was observed in our healthy aged and sporadic AD subjects, whereas the familial AD subjects lacked normal adaptation. The familial AD subjects also showed statistically significantly smaller peak amplitudes and shorter latencies of the N100 throughout the habituation test. This persistent difference in automatic habituation of sensory responses supports the view that different subtypes of AD are differentially affected. The observed differences give an objective measure of the impaired involuntary adaptive functions of neuronal networks involved in auditory processing in subtypes of AD. Since habituation reflects the most primitive stage of learning and short-term memory, altered habituation may predict faster deterioration of clinical status in the familial group of AD subjects.

Adaptation, Physiological↗
PubMed2001

Genome-wide linkage disequilibrium mapping of late-onset Alzheimer's disease in Finland.

BACKGROUND: AD is a complex neurodegenerative disorder comprising several disease-associated chromosome loci. To find novel susceptibility genes for late-onset AD, a population-based genome-wide search using linkage disequilibrium (LD) mapping approach has been performed. METHOD: Forty-seven patients with late-onset AD and 51 age-matched control subjects were carefully chosen from the same geographic area in eastern Finland, where the population is descended mainly from a small group of original founders. These subjects were initially genotyped with 366 polymorphic microsatellite markers, and a follow-up analysis was performed with additional microsatellite markers for those chromosome loci found to be associated with AD. RESULTS: Initial genome-wide screening revealed 21 chromosomal loci significantly associated with AD in addition to the 13q12 locus described previously. Subsequent comparison of single-allele frequencies of the microsatellite markers in the AD and control groups indicated the presence both of possible risk alleles (odds ratio [OR] > 1) and of possible protective alleles (OR < 1). Screening of the LD regions with additional microsatellite markers revealed seven chromosomal loci where more than one microsatellite marker was associated with AD (1p36.12, 2p22.2, 3q28, 4p13, 10p13, 18q12.1, and 19p13.3) in addition to the 13q12 locus. CONCLUSIONS: These genome-wide LD screening data suggest that several AD-associated chromosomal loci exist, which may encompass novel susceptibility genes for late-onset AD. Therefore, extensive screening of the genes located in the vicinity of these LD regions is necessary to elucidate their role in AD.

Age of Onset↗
PubMed2001

CLN3 protein is targeted to neuronal synapses but excluded from synaptic vesicles: new clues to Batten disease.

Batten disease (juvenile neuronal ceroid lipofuscinosis, JNCL), the most common neurodegenerative disease of childhood, is caused by mutations in the CLN3 gene encoding a putative transmembrane protein. The function of CLN3 is currently unknown but it has been shown to localize in the endosomal/lysosomal compartments of non-neuronal cells. In addition, several other intracellular localizations have been proposed and the controversy of the reports suggests that CLN3 may have different intracellular localization in different cell types. Batten disease severely affects neuronal cells but leaves other organs clinically unaffected, and thus it is of utmost importance to approach the disease mechanism by studying the expression and localization of CLN3 in the brain and neuronal cells. We have analysed here CLN3 in the mouse brain using in situ hybridization, immunohistochemical staining and western blot analysis of subcellular fractions. As visual deterioration is the hallmark of Batten disease we have set up primary retinal cultures from the mouse and analysed both endogenous mouse CLN3 and Semliki Forest virus-mediated human CLN3 localization using immunofluorescence staining and confocal microscopy. We demonstrate that CLN3 is abundantly expressed in neuronal cells, especially in the cortex, hippocampus and cerebellum of the adult mouse brain. Furthermore, our results indicate that in neurons CLN3 is not solely a lysosomal protein. It is localized in the synaptosomes but, interestingly, is not targeted to the synaptic vesicles. The novel localization of CLN3 directs attention towards molecular alterations at the synapses. This should yield important clues about the mechanisms of neurodegeneration in Batten disease.

Animals↗
PubMed2001

Palmitoyl protein thioesterase (PPT) localizes into synaptosomes and synaptic vesicles in neurons: implications for infantile neuronal ceroid lipofuscinosis (INCL).

A deficiency of palmitoyl protein thioesterase (PPT) leads to the neurodegenerative disease infantile neuronal ceroid lipofuscinosis (INCL), which is characterized by an almost complete loss of cortical neurons. PPT expressed in COS-1 cells is recognized by the mannose-6-phosphate receptor (M6PR) and is routed to lysosome, but a substantial fraction of PPT is secreted. We have here determined the neuronal localization of PPT by confocal microscopy, cryoimmunoelectron microscopy and cell fractionation. In mouse primary neurons and brain tissue, PPT is localized in synaptosomes and synaptic vesicles but not in lysosomes. Furthermore, in polarized epithelial Caco-2 cells, PPT is localized exclusively to the basolateral site, in contrast to the classical lysosomal enzyme, aspartylglucosaminidase (AGA), which is localized in the apical site. The current data imply that PPT has a role outside the lysosomes in the brain and may be associated with synaptic functioning. This finding opens a new route to study the neuropathological events associated with INCL.

Animals↗
PubMed2001

Heritability of leptin levels and the shared genetic effects on body mass index and leptin in adult Finnish twins.

OBJECTIVES: Leptin is involved in the regulation of body weight, but the relative role of genetic and environmental influences on inter-individual variation in leptin levels is unknown. DESIGN AND SUBJECTS: To investigate the genetic and environmental contributions to the association of body mass index (BMI) with serum leptin levels, 58 monozygotic (MZ, 27M, 31F), and 74 like-sexed dizygotic (DZ, 32M, 42F) Finnish twin pairs aged 50--76 y were studied. MEASUREMENTS: Serum leptin levels, weight, height, hip and waist measurements. RESULTS: Women had higher mean leptin levels (16.8+/-9.5 ng/ml), and more overall variability in leptin levels than men (6.4+/-3.5 ng/ml; P<0.0001). Leptin levels correlated highly with BMI in men and women. Among women, the MZ and DZ pairwise correlations for leptin were 0.41 (P=0.009) and 0.07 (P=0.32), respectively. Among men the MZ and DZ pairwise correlations for leptin were 0.47 (P=0.006) and 0.23 (P=0.10). Univariate twin analysis indicated that, among women, 34% and, among men, 45% of the variance in leptin can be attributed to additive genetic effects, and the remainder to unique environmental effects. Significant non-additive genetic or shared familial effects could not be demonstrated. A bivariate twin analysis of leptin and BMI indicated that the correlation between additive genetic effects on leptin and BMI was 0.79 (95% CI 0.68--0.86) in women, and 0.68 (0.51--0.80) in men. The correlation between environmental effects on leptin and BMI was 0.77 (95% CI 0.66--0.85) in women, and 0.48 (0.26--0.66) in men. CONCLUSION: Leptin levels are moderately heritable in older adults, and a substantial proportion of genetic effects are in common on leptin levels and obesity in both women and men. International Journal of Obesity (2001) 25, 132-137

Aged↗
PubMed2001

Assessment of beta-cell function during the oral glucose tolerance test by a minimal model of insulin secretion.

OBJECTIVE: To characterise the performance of beta-cell during a standard oral glucose tolerance test (OGTT). DESIGN: Fifty-six subjects were studied. A minimal analogic model of beta-cell secretion during the OGTT was applied to all OGTTs (see below). The amount of insulin secreted over 120' in response to oral glucose (OGTT-ISR; Insulin Units 120'-1 m-2 BSA) and an index of beta-cell secretory 'force' (beta-Index; pmol.min-2.m-2 BSA) were computed with the aid of the model. In protocol A, 10 healthy subjects underwent two repeat 75 g OGTT with frequent (every 10'-15') blood sampling for glucose and C-peptide to test the reproducibility of OGTT-ISR and beta-Index with a complete or a reduced data set. In protocol B, 7 healthy subjects underwent three OGTTs (50, 100 or 150 g), to test the stability of the beta-Index under different glucose loads. In protocol C, 29 subjects (15 with normal glucose tolerance, 7 with impaired glucose tolerance and 7 with newly diagnosed type 2 diabetes) underwent two repeat 75 g OGTT with reduced (every 30' for 120') blood sampling to compare the reproducibility and the discriminant ratio (DR) of OGTT-ISR and beta-index with the insulinogenic index (IG-Index: Delta Insulin 30' - Basal/Delta Glucose 30' - Basal). In protocol D, 20 subjects (14 with normal glucose tolerance, 5 with impaired glucose tolerance and 1 with newly-diagnosed type 2 diabetes) underwent a 75 g OGTT and an intravenous glucose tolerance test (IVGTT) on separate days to explore the relationships between acute (0'-10') insulin response (AIR) during the IVGTT and beta-index and OGTT-ISR during the OGTT. RESULTS: In all protocols, the minimal analogic model of C-peptide secretion achieved a reasonable fit of the experimental data. In protocol A, a good reproducibility of both beta-index and OGTT-ISR was observed with both complete and reduced (every 30') data sets. In protocol B, increasing the oral glucose load caused progressive increases in OGTT-ISR (from 2.63 +/- 0.70 to 5.11 +/- 0.91 Units.120'-1.m-2 BSA; P < 0.01), but the beta-index stayed the same (4.14 +/- 0.35 vs. 4.29 +/- 0.30 vs. 4.30 +/- 0.33 pmol.min-2.m-2 BSA). In protocol C, both OGTT-ISR and beta-index had lower day-to-day CVs (17.6 +/- 2.2 and 12.4 +/- 2.4%, respectively) and higher DRs (2.57 and 1.74, respectively) than the IG-index (CV: 35.5 +/- 6.3%; DR: 0.934). OGTT-ISR was positively correlated to BMI (P < 0.03), whereas beta-index was inversely related to both fasting and 2 h plasma glucose (P < 0.01 for both). In protocol D, beta-index, but not OGTT-ISR, was significantly correlated to AIR (r = 0.542, P < 0.02). CONCLUSIONS: Analogically modelling beta-cell function during the OGTT provides a simple, useful tool for the physiological assessment of beta-cell function.

Adult↗
PubMed2001

Metabolic impact of a family history of Type 2 diabetes. Results from a European multicentre study (EGIR).

BACKGROUND: Insulin resistance was found in some but not in all previous studies of non-diabetic first degree relatives of Type 2 diabetic patients. Small study groups, ethnic differences and/or non-optimal techniques may explain the conflicting results. AIM: To study the impact of a family history of Type 2 diabetes on insulin action in a large group of non-diabetic Europeans using the 'gold standard' euglycaemic hyperinsulinaemic clamp technique. METHODS: Non-diabetic subjects (n = 235) with a positive family history of Type 2 diabetes (FH+) and 564 subjects with no family history of diabetes (FH-) were recruited from The European Group of Insulin Resistance (EGIR) database. This database includes measurements of insulin action using the insulin clamp technique (1 mU/kg per min) in normal glucose-tolerant individuals from 20 different European centres. In a subset of subjects the measurements were performed in combination with indirect calorimetry (n = 80 vs. 213 with and without family history of Type 2 diabetes). RESULTS: The body mass index (BMI) was slightly higher in FH+ compared with FH- (26.7 +/- 4.6 vs. 25.1 +/- 4.7 kg/m(2); P < 0.02). After correction for covariates according to differences between investigators and subject characteristics including BMI (multiple regression analysis), insulin-stimulated glucose disposal was lower in FH+ compared with FH- (P < 0.00001). Insulin-stimulated glucose oxidation was slightly increased in FH+ compared with FH-, and insulin-stimulated non-oxidative glucose metabolism was consequently markedly reduced in FH+ compared with FH- (P < 0.0005). CONCLUSION: Insulin resistance is present in European non-diabetic relatives of Type 2 diabetic patients. The insulin resistance is independent of degree of obesity and is restricted solely to the pathway of non-oxidative glucose metabolism. Diabet. Med. 18, 533-540 (2001)

Adult↗
PubMed2001

Metabolic effects of metformin in patients with impaired glucose tolerance.

AIMS: To assess the effect of metformin on insulin sensitivity, glucose tolerance and components of the metabolic syndrome in patients with impaired glucose tolerance (IGT). METHODS: Forty first-degree relatives of patients with Type 2 diabetes fulfilling WHO criteria for IGT and participating in the Botnia study in Finland were randomized to treatment with either metformin 500 mg b.i.d. or placebo for 6 months. An oral glucose tolerance test (OGTT) and a euglycaemic hyperinsulinaemic clamp in combination with indirect calorimetry was performed at 0 and 6 months. The patients were followed after stopping treatment for another 6 months in an open trial and a repeat OGTT was performed at 12 months. RESULTS: Metformin treatment resulted in a 20% improvement in insulin-stimulated glucose metabolism (from 28.7 +/- 13 to 34.4 +/- 10.7 micromol/kg fat-free mass (FFM)/min) compared with placebo (P = 0.01), which was primarily due to an increase in glucose oxidation (from 16.6 +/- 3.6 to 19.1 +/- 4.4 micromol/kg FFM; P = 0.03) These changes were associated with a minimal improvement in glucose tolerance, which was maintained after 12 months. CONCLUSIONS: Metformin improves insulin sensitivity in subjects with IGT primarily by reversal of the glucose fatty acid cycle. Obviously large multicentre studies are needed to establish whether these effects are sufficient to prevent progression to manifest Type 2 diabetes and associated cardiovascular morbidity and mortality. Diabet. Med. 18, 578-583 (2001)

Blood Glucose↗
PubMed2001

A gene conferring susceptibility to type 2 diabetes in conjunction with obesity is located on chromosome 18p11.

Genome-wide nonparametric linkage analysis of 480 sib-pairs affected with type 2 diabetes revealed linkage to a previously unreported susceptibility locus on chromosome 18p11. This result improved with stringent subphenotyping using age- and sex-adjusted BMI, ultimately reaching a logarithm of odds of 3.82 (allele sharing 0.6654) at a point between markers D18S976 and D18S391 when the most obese 20% of the sample was analyzed. Several genes on chromosome 18 have been suggested as metabolic disease candidates, but none of these colocalize with our linkage result. We conclude that our results provide support for the presence of a currently uncharacterized gene on chromosome 18p, certain alleles of which confer increased susceptibility to type 2 diabetes in conjunction with obesity. We additionally observed moderate evidence for linkage to chromosome 1, near marker D1S3462; chromosome 4, near marker D4S2361; chromosome 5, near marker D5S1505; and chromosome 17, near marker D17S1301.

Adult↗
PubMed2000

MPO and APOEepsilon4 polymorphisms interact to increase risk for AD in Finnish males.

BACKGROUND: Myeloperoxidase (MPO) is present in senile plaques and surrounding reactive microglia, but not in normal brain parenchyma. MPO in plaques is highest in APOE epsilon4 carriers, suggesting a functional interaction. An MPO promoter polymorphism (-463G/A) linked to increased MPO expression has been associated with increased risk of AD. METHODS: To further define the possible interaction of MPO and APOE epsilon4, we examined 127 patients with AD and 174 controls from a genetically homogeneous Finnish population. RESULTS: A significantly higher percentage of male patients with AD carried the MPO A and APOE epsilon4 alleles relative to men carrying neither allele (p < 0.001; OR, 11.4; 95% CI, 3.6 to 6.7). Male APOE epsilon4 carriers lacking the MPO A allele had an OR of 3.0 (p = 0.01; 95% CI, 1.3 to 6.9), indicating that MPO A enhances AD risk by 3.8-fold. Age at onset was lower in men carrying the MPO A and APOE epsilon4 alleles (Kaplan-Meier survival analysis; p = 0.01). Also, the MPO AA genotype was associated with selective mortality in men, but not in women. AA genotypes were absent from 159 male patients with AD and controls, representing the expected 5% to 6% in women and male controls younger than age 20. The -463A creates an estrogen receptor binding site that may contribute to these gender differences. CONCLUSIONS: MPO A and APOE epsilon4 alleles interact to increase the risk of AD in men but not in women in this Finnish cohort.

Age of Onset↗
PubMed2000

Hippocampus in Alzheimer's disease: a 3-year follow-up MRI study.

BACKGROUND: Due to the progressive nature of Alzheimer's disease (AD), it has been proposed that serial imaging studies tracking the course of progression might improve the diagnostic accuracy of AD. METHODS: Longitudinal changes in hippocampal volumes were evaluated using magnetic resonance imaging (MRI) over a period of 3 years in 27 AD patients and 8 control subjects. RESULTS: A statistically nonsignificant trend towards accelerated volume loss in the AD group compared to control subjects was observed. During the study period, the average shrinkage of the hippocampal volume ranged from -2.2% to -5.8% in control subjects, and from -2.3% to -15.6% in AD patients. CONCLUSIONS: The observed changes at an individual level were small, and within the accuracy range of the measurements. Therefore, serial MRI of the hippocampus did not offer any advantage over a single MRI to support the diagnosis of AD in this study sample.

Aged↗
PubMed2000

Is the presenilin-1 E318G missense mutation a risk factor for Alzheimer's disease?

Nearly all of the presenilin-1 (PSEN-1) mutations are missense mutations leading to Alzheimer's disease (AD). The role of the mutation E318G (a substitution of glutamic acid to glycine) in the PSEN-1 is controversial. It has been found both in AD patients and in non-demented control individuals. Using the polymerase chain reaction and the restriction fragment length polymorphism method, we screened for E318G mutation in a total of 16 familial (FAD) cases, in 64 sporadic neuropathologically confirmed AD cases and in 270 non-demented controls including 35 neuropathologically confirmed individuals. We detected the E318G mutation in four FAD cases, seven sporadic AD cases and 10 control individuals with highly varying onset-ages. Odds ratios for carrying the mutation were 7.6 and 3 in FAD and sporadic AD cases, respectively. Our results suggest that this mutation could be a risk factor in the Finnish FAD and sporadic AD population. It may be in linkage disequilibrium with a pathogenic change somewhere else in the PSEN-1 gene or in close proximity to the PSEN-1 gene.

Aged↗
PubMed2000

Insulin sensitivity and insulin secretion in monozygotic and dizygotic twins.

AIMS/HYPOTHESIS: To estimate the heritability of insulin sensitivity and insulin secretion, both of which are considered to contribute to the development of Type II (non-insulin-dependent) diabetes mellitus. METHODS: Intraclass correlation coefficients and heritability estimates for insulin sensitivity (euglycaemic clamp) as well as first-phase and late-phase insulin secretion (intravenous glucose tolerance test) were calculated in 21 monozygotic and 20 dizygotic twin pairs of the same sex between 54 and 72 years of age. RESULTS: Intrapair correlations for all traits were consistently higher in monozygotic than in dizygotic pairs. Insulin secretion correlated significantly only between monozygotic (first-phase r = 0.55; p = 0.003 and late-phase r = 0.66; p < 0.001) twins giving heritability estimates of 0.55 and 0.58, respectively. Insulin-stimulated glucose uptake showed a more modest correlation between monozygotic twins (r = 0.46; p = 0.015). The heritability estimate was 0.37. The heritability estimate for waist-to-hip ratio was 0.76 in female and 0.70 in male twins. CONCLUSION/INTERPRETATION: Genetic variability seems to contribute to the variance of insulin sensitivity as well as of insulin secretion. In the current study, genetic variance accounted almost 60% for the variance in glucose-stimulated insulin secretion and almost 40% for the variance in insulin-stimulated glucose uptake. Our data is also compatible with findings in monogenic forms of diabetes in which genetic defects in insulin secretion play a predominant part in the pathogenesis of hyperglycaemia.

Aged↗
PubMed2000

Identification of a novel 4.6-kb genomic deletion in presenilin-1 gene which results in exclusion of exon 9 in a Finnish early onset Alzheimer's disease family: an Alu core sequence-stimulated recombination?

Mutations in the presenilin-1 (PS-1) gene have been shown to cause early onset Alzheimer's disease (EOAD) in an autosomal dominant manner. We have identified a novel 4.6-kb genomic deletion in the PS-1 gene in a Finnish EOAD family, which leads to an inframe exclusion of exon9 (delta9) from the mRNA transcript. This germline mutation results in a similar alteration in mRNA level as previously described with the variant AD and the delta9 splice-site mutations. In this present EOAD family, the clinical and neuropathological phenotype of patients are those of the typical AD without indications of spastic paraparesis or 'cotton wool' plaques, which are the hallmarks of the variant AD. A sequence analysis of the deletion crossover site of the mutant and corresponding wild type regions revealed complete homology with the recombigenic 26 bp Alu core sequence at intron 8. In addition, a segment at the intron 9 breakpoint displayed homology with the core sequence, but comparison of the 5' and 3' breakpoint sequences did not reveal significant identity favouring involvement of Alu core sequence-stimulated non-homologous recombination rather than Alu-mediated homologous pairing of the fragments. This study shows that large genomic rearrangements can affect the EOAD gene PS-1 through a mechanism, which may involve Alu core sequence-stimulated recombination.

Age of Onset↗
PubMed2000

The decrease in luteinizing hormone secretion in response to weight reduction is inversely related to the severity of insulin resistance in overweight women.

Controversial effects of weight reduction on gonadotropin secretion in obesity have been reported. As a result of pulsatility, single serum samples or frequent sampling studies are somewhat limited with regard to monitoring LH and FSH concentrations. We studied follicular phase nocturnal urinary (nu) LH and FSH secretion and glucose metabolism (150-min euglycemic hyperinsulinemic clamp) during 1 menstrual cycle/30-day period before and after weight reduction in 10 severely overweight infertility patients (age, 29 +/- 3.1 yr; body mass index, 37.1 +/- 3.3 kg/m2; +/-SEM). A 6-week very low calorie diet was followed by a 4-week normocaloric period. The urinary LH and FSH results reported represent samples taken 12 to 2 days before the LH surge, or 10 consecutive samples in the case of amenorrhea. We observed a decrease of 8% (P < 0.001) in percent body fat mass and a 5% (P < 0.005) reduction in waist to hip ratio. Mean nu-LH decreased by 45% [6.06 +/- 1.05 (+/-SEM) to 3.22 +/- 0.71 IU/L], whereas mean nu-FSH remained unchanged. Insulin-stimulated glucose uptake increased by 41% (P < 0.01), which was accounted for by a significant increase in nonoxidative glucose disposal (P = 0.003). Serum sex hormone-binding globulin concentrations increased by 39% (P < 0.01), and insulin-like growth factor (IGF)-binding protein-1 (IGFBP-1) levels increased by 46% (P < 0.05). Fasting serum insulin concentrations decreased by 38%, those of leptin by 37%, those of androstenedione by 32%, those of testosterone by 20% (all P < 0.01), and those of dehydroepiandrosterone sulfate by 13% (P < 0.05). The percent change in nu-LH correlated negatively with glucose uptake (r = -0.76; P < 0.01) and the increase in serum sex hormone-binding globulin (r = -0.85; P < 0.005) and positively with the percent change in waist to hip ratio (r = 0.79; P < 0.01). The absolute nu-LH levels after weight reduction correlated significantly with fasting insulin concentrations (r = 0.88; P < 0.001) and negatively with glucose uptake (r = -0.67; P < 0.05). No significant relationships were found between absolute levels or changes in nu-LH concentrations and leptin, IGF-I, IGFBP-3, or IGFBP-1 concentrations. Our findings suggest that weight reduction with a very low calorie diet results in a decrease in nu-LH concentrations, a reduction in the LH/FSH ratio, and FSH predominance favoring folliculogenesis. The decrease in LH concentrations is inversely related to the severity of insulin resistance. It is possible that the decrease in LH secretion with weight reduction is more dependent on the absolute levels of insulin sensitivity than on the degree of general adiposity.

Adult↗
PubMed1999

Functional consequences of amyloidosis mutation for gelsolin polypeptide -- analysis of gelsolin-actin interaction and gelsolin processing in gelsolin knock-out fibroblasts.

Gelsolin, an actin-modulating protein, derived from a single gene exists in intracellular and secreted forms. A point mutation at position 187 of both forms of gelsolin causes familial amyloidosis of the Finnish type (FAF). Here, we expressed both isoforms of the wild-type and FAF mutant gelsolin in mouse embryonic gelsolin-null fibroblasts. We demonstrate that the FAF mutation does not interfere with the normal actin-modulating function of intracellular gelsolin, and that aberrant processing of secreted FAF gelsolin to FAF amyloid precursor takes place in the gelsolin-negative background. These results suggest that, in patients with FAF, symptoms are caused by the accumulation in their tissues of amyloid derived from plasma gelsolin and are not due to functional differences in cytoplasmic gelsolin.

Actins↗