Protease inhibitor domain encoded by an amyloid protein precursor mRNA associated with Alzheimerʼs disease

Tanzi, R.E.; McClatchey, Andrea I.; Lamperti, Edward D.; Villa‐Komaroff, Lydia; Gusella, James F.; Neve, Rachael L.

doi:10.1097/00002093-198802040-00013

Cited by 8 publications

(8 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…They correspond to translation products of APP 695 mRNA as was confirmed by RNA analysis (results not shown). These findings are in accordance with results from other groups who were able to show, that APP 695 is the predominantly expressed form in neurons [3,4,6,8,9,31].…”

Section: Metabolic Characterizationsupporting

confidence: 93%

APP Expression in Primary Neuronal Cell Cultures fromP6 Mice during in vitro Differentiation

Dichgans

Mönning

König

et al. 1993

Dement Geriatr Cogn Disord

View full text Add to dashboard Cite

Primary neuronal cell cultures from P6 mice were investigated in order to study amyloid protein precursor (APP) gene expression in differentiating neurons. Cerebellar granule cells which strongly express APP 695 allowed the identification of three distinct isoforms of neuronal APP 695. The high-molecular-weight form of APP 695 is sialylated. The expression pattern of neuronal APP 695 changes during in vitro differentiation. Sialylated forms become more abundant upon longer cultivation time. The secreted forms of sialylated, neuronal APP 695 are shown to comigrate with APP isolated from cerebrospinal fluid. We suggest that the different sialylation states of APP 695 may reflect the modulation of cell-cell and cell-substrate interactions during in vitro differentiation and regeneration.

show abstract

Section: Metabolic Characterizationsupporting

confidence: 93%

APP Expression in Primary Neuronal Cell Cultures fromP6 Mice during in vitro Differentiation

Dichgans

Mönning

König

et al. 1993

Dement Geriatr Cogn Disord

View full text Add to dashboard Cite

show abstract

“…1 The primary constituent of amyloid plaques is a 39-43 aminoacid hydrophobic peptide, named A␤, which is produced as the cleavage product of a much larger protein, the amyloid precursor protein (APP). 2,3 Cleavage of APP is complex and can be regulated by several protease activities. The pathways that generate A␤ (reviewed in Racchi and Govoni 4 ) are regulated by the sequential action of two enzymes, named ␤ and ␥-sec-retase.…”

Section: Introductionmentioning

confidence: 99%

Short- and long-term effect of acetylcholinesterase inhibition on the expression and metabolism of the amyloid precursor protein

et al. 2001

View full text Add to dashboard Cite

We have investigated the acute and chronic effect of metrifonate (MTF) and dichlorvos (DDVP), respectively the prodrug and active acetylcholinesterase inhibitor, on the secretory processing of the amyloid precursor protein (APP) in SH-SY5Y neuroblastoma cells. We demonstrate that the acute treatment of SH-SY5Y cells with both compounds results in an increased secretion of the soluble fragment of APP (sAPP␣) into the conditioned media of cells, with a pattern correlated to the level of acetycholinesterase inhibition. The regulation of APP processing in these conditions is mediated by an indirect cholinergic effect on muscarinic receptors, as demonstrated by inhibition with atropine. We have also followed APP expression and metabolism after long-term treatment with metrifonate. Treated cells showed reduced AChE activity after 24, 48 h and also following 7 days of repeated treatment, a time point at which increased AChE expression was detectable. At all time points sAPP␣ release was unaffected suggesting that enhanced sAPP␣ release by MTF is transitory, nevertheless the sensitivity of cholinergic receptors was unchanged, as indicated by the fact that cholinergic response can be elicited similarly in untreated and treated cells. APP gene expression was unaffected by long-term AChE inhibition suggesting that increased short-term sAPP␣ release does not elicit compensatory effects. Molecular Psychiatry (2001) 6, 520-528.

show abstract

“…However, to date, DNA markers have been mapped to chromosome 21 in only a few such families with early onset dementia [St. George-Hyslop et al, 1987;Marx, 1988;Goate et al, 19891. Initially, the B-amyloid gene was believed to be a candidate gene for FAD [Goodfellow, 1987;Tanzi et al, 1987a1, but further investigation has shown this not to be the case [Tanzi et al, 1987b;Van Broekhoven et al, 1987;Devine-Gage et al, 1988;Schellenberg et al, 19881, although the role of the amyloid precursor protein in plaque formation is still under investigation [Ponte et al, 1988;Tanzi et al, 1988;Kitaguchi et al, 19881. With respect to clinical, pathological, and biochemical features, the FAD phenotype cannot be clearly distinguished from "sporadic" cases.…”

Section: Introductionmentioning

confidence: 99%

Genetic studies on an Alzheimer Clinic population

Sadovnick

et al. 1989

Genetic Epidemiology

View full text Add to dashboard Cite

All patients attending the Clinic for Alzheimer Disease and Related Disorders have detailed family histories taken by a geneticist. To date, genetic histories are available for 446 consecutive, unrelated individuals. Of these, 151 (33.9%) are diagnosed as having "probable" (N = 141) or "autopsy-confirmed" (N = 10) Alzheimer disease according to recognized criteria. This data base represents a relatively unselected population with respect to more than one person in the family having dementia. Seventy-one of these 151 index cases (47.0%) have a positive family history of dementia, of which 8 (5.3%) may represent the familial (autosomal dominant) form of Alzheimer disease (FAD). Age-corrected empiric recurrence risks for Alzheimer disease/dementia were calculated for first-degree relatives of these 151 index cases using the Kaplan-Meier lifetable method.

show abstract

Protease inhibitor domain encoded by an amyloid protein precursor mRNA associated with Alzheimerʼs disease

Cited by 8 publications

References 0 publications

APP Expression in Primary Neuronal Cell Cultures fromP6 Mice during in vitro Differentiation

APP Expression in Primary Neuronal Cell Cultures fromP6 Mice during in vitro Differentiation

Short- and long-term effect of acetylcholinesterase inhibition on the expression and metabolism of the amyloid precursor protein

Genetic studies on an Alzheimer Clinic population

Contact Info

Product

Resources

About