ABSTRACT
We have recently discovered in Torino (Italy) a new pedigree with early-onset Alzheimer's disease. The index patient is a woman who, at the age of 43 years, showed progressive memory impairment and ideomotor apraxia. Several relatives of the patient have had a history of dementia. The ancestors of the patient were from Calabria (southern Italy) and members of the family emigrated to the north of Italy, to France, and to the United States. Up to now, the new kindred comprises 1950 members, distributed in eight generations. Thirty members affected with Alzheimer's disease have been identified. Neuropathologic confirmation of antemortem clinically diagnosed Alzheimer's disease has been achieved for one patient. The pedigree is consistent with autosomal dominant inheritance. The clinical course of the disease is fairly uniform: the first symptom is memory loss, beginning around age 40 years. Psychiatric symptoms like hallucinations and delusions follow. At a later stage of the disease, several patients developed myoclonus and generalized epileptic seizures and eventually died with profound dementia. The "Torino family" shows several genealogic and clinical similarities with other large multigenerational familial Alzheimer's disease pedigrees originating from the Calabria region.
Subject(s)
Alzheimer Disease/genetics , Adult , Age Factors , Alzheimer Disease/diagnosis , Alzheimer Disease/psychology , Female , Humans , Italy , Male , Middle Aged , Models, Genetic , Neuropsychological Tests , PedigreeABSTRACT
Several kindreds (N, C, To and RB) with familial Alzheimer disease (FAD) from the same small area of Calabria are currently under study. Recently two of us (F.M. and L.F-S.) identified a family in Milan (FJ01) made up of 3 siblings whose parents were of Calabrian origin. Through a subsequent systematic or blanket genealogical study a link has been traced between kindreds To and FJ01. We discuss the relevance of these results to genetic studies.
Subject(s)
Alzheimer Disease/genetics , Adult , Alzheimer Disease/physiopathology , Alzheimer Disease/psychology , Female , Humans , Male , PedigreeABSTRACT
In an Italian kindred (family N), early onset Alzheimer's disease has been transmitted in a Mendelian autosomal fashion since the early 18th century. The age at death of affected members of the family varies widely, and was taken as an index of the age of expression, a measure of phenotypic variability. Either a gamma or a log-normal algorithm provides the best fit for the age at death distribution. Subsets of family N widely different as to time and place have the same age at death of patients: Environment appears to play a negligible role in the expression of disease. Pairwise correlation between an affected parent and child is zero: The disease is monogenic (no major expression gene). The same stochastic distribution of age of expression, but with late onset, and after correction for death from other causes, is compatible with the epidemiology of Alzheimer's disease in general. Mendelian genetics is a possible model for Alzheimer's disease etiology.
Subject(s)
Alzheimer Disease/genetics , Gene Expression Regulation/physiology , Phenotype , Adult , Age Factors , Aged , Alzheimer Disease/diagnosis , Alzheimer Disease/psychology , Atrophy , Brain/pathology , Humans , Male , Middle Aged , Models, Statistical , Risk FactorsABSTRACT
We report the genealogical, clinical and molecular genetic findings of a new family with autosomal dominant early-onset Alzheimer's disease (FAD) discovered in Torino (Italy). Up to now, the pedigree comprises 1500 members, distributed in 8 generations. 22 patients affected with Alzheimer's disease have been identified. The clinical course of the disease was fairly uniform in all the patients. An high incidence of myoclonic jerks and epileptic seizures was found. Molecular genetic studies showed the presence of positive but nonsignificant lod scores between chromosome 21 anonymous DNA markers and the disease. The data obtained from the Torino family were computed together with those of additional 47 pedigrees, with both early-onset and late-onset Alzheimer's disease. A predisposing locus for the disease was found on the pericentromeric region of chromosome 21 only in early-onset FAD pedigrees.
Subject(s)
Alzheimer Disease/genetics , Phenotype , Adult , Alzheimer Disease/diagnosis , Chromosome Aberrations/genetics , Chromosome Disorders , Female , Genes, Dominant/genetics , Genetic Carrier Screening , Genetic Markers/genetics , Humans , ItalyABSTRACT
An established anterior cruciate ligament deficiency-induced articular cartilage degeneration was used to evaluate the effects of intrasynovial injection of hyaluronic acid upon cartilage destruction. In this study, proteoglycan solubility under associative and dissociative conditions was compared in two treatment protocols at intervals of seven, 13, and 17 weeks after surgical breakage of the anterior cruciate ligament in 2.5-year-old Beagle dogs. Untreated joints showed a marked increase in both total soluble glycosaminoglycan (GAG measured as uronic acid) and in the associative fraction. In both treated groups, there was a reduced amount of soluble GAG. Cessation of treatment after seven weeks caused gradual regression, with an increasing amount of CaCl2-soluble material in the associative fraction, while inception at seven weeks gave biochemical evidence of reversal, with increasing GAG present in the guanidine-soluble (dissociative) fraction on the insoluble residue. The protective effects of hyaluronic acid suggest the potential clinical application of this therapy in retarding the advance of osteoarthritis.
