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Biomedical subjects

B Borroni

Publications and source records attributed to B Borroni.

26 records · Page 2Linked to original sources
PubMed2001

Amyloid precursor protein in platelets: a peripheral marker for the diagnosis of sporadic AD.

BACKGROUND: An altered pattern of amyloid precursor protein (APP) forms consisting in a reduced ratio between the upper (130 kDa) and the lower (106 to 110 kDa) immunoreactivity bands has been described in platelets of patients with AD. OBJECTIVE: To evaluate the sensitivity and the specificity of platelet APP forms' ratio (APPr) as a marker for AD. METHODS: Eighty-five patients with probable AD and 95 control subjects (CON), including healthy individuals and neurologic patients, entered the study. Platelet APPr was evaluated by means of Western Blot analysis and immunostaining in the whole platelet homogenate, and calculated by the ratio between the optical density (OD) of the upper (130 kDa) and the lower (106 to 110 kDa) APP immunoreactive bands. RESULTS: Mean APPr levels were decreased in AD patients (mean OD +/- SD = 0.35 +/- 0.18) compared with the CON group (mean OD +/- SD = 0.92 +/- 0.38) (DF 1, 178, p < 0.0001). Accuracy levels measured by Receiver Operating Curve analysis showed that a cut-off level of 0.57 resulted in a sensitivity of 88.2% and a specificity of 89.4%, with an area under the curve of 0.945. APPr levels were significantly associated with disease severity (mild AD versus moderate AD: p < 0.0001; moderate AD versus severe AD: p < 0.05). CONCLUSION: Platelet APPr allowed to differentiate AD from normal aging and other dementing disorders with high sensitivity and specificity. These findings suggest that platelet APPr may be of help as an adjunctive diagnostic tool in clinical practice.

Aged↗
PubMed2001

Amyloid precursor protein in platelets of patients with Alzheimer disease: effect of acetylcholinesterase inhibitor treatment.

BACKGROUND: Amyloid precursor protein (APP) forms with apparent molecular weights of 130, 110, and 106 kd are present in human platelets. It has been demonstrated that Alzheimer disease (AD) is specifically associated with a decreased APP forms ratio in platelets. OBJECTIVE: To investigate whether acetylcholinesterase (AChE) inhibitor treatment modifies the ratio of platelet APP forms in patients with AD. PATIENTS AND METHODS: From a large sample of patients with probable AD, 30 with mild to moderate AD were selected. Each patient underwent a clinical evaluation including the Mini-Mental State Examination (MMSE) and platelet APP forms analysis at baseline and after 30 days. During this interval, 20 of 30 patients with AD were treated with donepezil hydrochloride (5 mg/d), a piperidine phosphate-based cholinesterase inhibitor. Platelets were subjected to Western blot analysis using monoclonal antibody (22C11). The ratio between the immunoreactivity of the higher-molecular-weight APP form (130 kd) and the lower forms (106 and 110 kd) was measured. RESULTS: All patients taking donepezil completed the 30 days of treatment without adverse effects. The platelet APP forms ratio at baseline did not differ between the 2 AD groups (mean +/- SD optical density ratio: untreated AD, 0.47 +/- 0.12; treated AD, 0.38 +/- 0.18), whereas a significant difference was found at follow-up (mean +/- SD optical density ratio: untreated AD, 0.45 +/- 0.17; treated AD, 0.77 +/- 0.29; P<.001). A significant improvement in MMSE scores in treated AD patients was observed from baseline (16.9 +/- 3.8) to 30 days (18.9 +/- 4.42) (P<.009, 30 days vs baseline), but no significant correlation was found in treated AD patients between MMSE score improvement and APP forms/ratio increase (P =.09). CONCLUSIONS: Administration of AChE inhibitors increases the ratio of APP forms in platelets of patients with AD, suggesting a potential effect of AChE inhibitors on APP trafficking or processing in a peripheral cell.

Aged↗
PubMed2001

Lemierre's syndrome complicated by carotid thrombosis.

Lemierre's syndrome, also known as postanginal sepsis, is a rare condition that presents as an increasing sore throat due to acute pharyngitis or tonsillitis and progresses to sepsis, due to suppurative thrombophlebitis of the internal jugular vein. We present an atypical case of Lemierre's syndrome complicated by carotid thrombosis. The etiological factors and the diagnostic and therapeutic measures are discussed.

Adult↗
PubMed2001

Platelet amyloid precursor protein forms in AD: a peripheral diagnostic tool and a pharmacological target.

Alzheimer Disease (AD) is characterized by the progressive deposition of beta-amyloid in the parenchyma and cerebral microvasculature. The beta-amyloid peptide derives from the metabolism of a larger precursor, Amyloid Precursor Protein (APP). This protein is present in central nervous system, but it is also expressed in peripheral tissues such as circulating cells. An alteration of the APP forms pattern in platelets has been recently reported in AD patients when compared to platelets both of control subjects or non AD patients (NADD). The accuracy of the assay to identify AD is high and decreased levels are found throughout the course of AD with a significant association with severity of symptoms. Moreover, a recent study has demonstrated that AD patients on donepezil (5 mg daily) for 4 weeks displayed two-fold increase in their APPr baseline levels up to normal range. Thus, platelet APP ratio (APPr) holds the potential to be a clinical marker, which might be of helpful and adjunctive value in the diagnosis of AD and in tracking the course of illness, also in the early stages when pharmacological treatment has the greatest potential of being effective.

Alzheimer Disease↗
PubMed2000

Platelets as a peripheral district where to study pathogenetic mechanisms of alzheimer disease: the case of amyloid precursor protein.

Alzheimer disease is a progressive neurodegenerative disease, characterised by a progressive cognitive and memory decline. From a neuropathological point of view, Alzheimer disease is defined by the presence of characteristic lesions, i.e. mature senile plaques, neurofibrillary tangles (NFTs) and amyloid angiopathy. In particular, accumulation of the amyloid beta-peptide in the brain parenchyma and vasculature is an invariant event in the pathogenesis of both sporadic and familial Alzheimer cases. Amyloid beta-peptide originates from a larger precursor, the amyloid precursor protein (APP) ubiquitously expressed. Among the different peripheral cells expressing APP forms, platelets are particularly interesting since they show concentrations of its isoforms equivalent to those found in brain. Moreover, a number of laboratories independently described alterations in APP metabolism/concentration in platelets of Alzheimer patients when compared to control subjects matched for demographic characteristics. These observations defined the frame of our work aimed to investigate if a correlation between levels of platelet APP forms and Alzheimer disease could be detected. We have reported that patients affected by Alzheimer disease show a differential level of platelet APP forms. This observation has several implications: APP processing abnormalities, believed to be a very early change in Alzheimer disease in neuronal compartment, do occur in extraneuronal tissues, such as platelets, thus, suggesting that Alzheimer disease is a systemic disorder; further, our data strongly indicate that a differential level of platelet APP isoforms can be considered a potential peripheral marker of Alzheimer disease allowing for discrimination between Alzheimer and other types of dementia.

Alzheimer Disease↗
PubMed2000

Presenilin 2 mutation does not influence expression and concentration of APP forms in human platelets.

BACKGROUND: The pattern of platelet amyloid precursor protein (APP) forms is altered in sporadic Alzheimer's disease patients, compared with both control subjects and non-Alzheimer's disease-demented patients. The aims of this study were to evaluate in platelets of symptomatic and presymptomatic patients carrying the mutation Met239Val in presenilin 2 (PS2) whether: i) PS2 and presenilin 3 (PS1) were expressed in platelets; ii) an altered expression of different APP isoforms mRNAs could be related to the presence of the mutation; and iii) an abnormal pattern of APP forms was associated to the mutation. MATERIALS AND METHODS: Reverse transcriptionpolymerase chain reaction (RT-PCR) of APP isoforms, PS1 and PS2 was performed on RNA extracted from platelets of three PS2 Met239Val mutated subjects, seven sporadic Alzheimer's patients and nine control subjects. The pattern of platelet APP forms at protein level was evaluated in the same population of subjects by means of Western blots analysis with specific antibody. RESULTS: We found that PS1 and PS2 were expressed correctly in human platelets. When the relative amount of expression of mRNA coding for APP 771/ 751-695 was measured, a similar ratio of expression was found in PS2-mutated subjects, compared with both sporadic Alzheimer's patients and to control subjects. Furthermore, when APP forms were evaluated in platelet homogenates by means of Western blots analysis with appropriate antibody, no difference was found in the pattern of APP forms in presence of PS2 mutation in platelets, compared with control subjects. CONCLUSIONS: These results indicated that PS2 was expressed in human platelets and that PS2 mutation did not affect APP forms pattern, thus, suggesting that in this peripheral cell the pathological effect of PS2 mutation might occur upstream of the amyloid cascade.

Aged↗
PubMedDate not supplied

Peripheral blood abnormalities in Alzheimer disease: evidence for early endothelial dysfunction.

Clinical and epidemiologic studies demonstrate that vascular risk factors may be involved in Alzheimer disease (AD). To evaluate whether vascular abnormalities are an early feature of AD, several parameters of coagulation and fibrinolysis were assessed. Thirty patients with mild AD and 30 age-matched control subjects entered the study. All subjects performed a standardized clinical and laboratory protocol. Persons with vascular risk factors and systemic diseases were excluded. AD patients present significant increased levels of thrombomodulin (p < 0.0001) and sE-selectin (p < 0.03). In contrast, no difference was found between the two diagnostic groups in the levels of beta-thromboglobulin, prothrombin fragment 1+2, fibrinogen, and von Willebrand factor. No other association but diagnosis was found with thrombomodulin and sE-selectin. These findings suggest that endothelial dysfunction is an early event in AD patients.

Aged↗