Rare Variants in APP, PSEN1 and PSEN2 Increase Risk for AD in Late-Onset Alzheimer's Disease Families

Pathogenic mutations in APP, PSEN1, PSEN2, MAPT and GRN have previously been linked to familial early onset forms of dementia. Mutation screening in these genes has been performed in either very small series or in single families with late onset AD (LOAD). Similarly, studies in single families have reported mutations in MAPT and GRN associated with clinical AD but no systematic screen of a large dataset has been performed to determine how frequently this occurs. We report sequence data for 439 probands from late-onset AD families with a history of four or more affected individuals. Sixty sequenced individuals (13.7%) carried a novel or pathogenic mutation. Eight pathogenic variants, (one each in APP and MAPT, two in PSEN1 and four in GRN) three of which are novel, were found in 14 samples. Thirteen additional variants, present in 23 families, did not segregate with disease, but the frequency of these variants is higher in AD cases than controls, indicating that these variants may also modify risk for disease. The frequency of rare variants in these genes in this series is significantly higher than in the 1,000 genome project (p = 5.09×10−5; OR = 2.21; 95%CI = 1.49–3.28) or an unselected population of 12,481 samples (p = 6.82×10−5; OR = 2.19; 95%CI = 1.347–3.26). Rare coding variants in APP, PSEN1 and PSEN2, increase risk for or cause late onset AD. The presence of variants in these genes in LOAD and early-onset AD demonstrates that factors other than the mutation can impact the age at onset and penetrance of at least some variants associated with AD. MAPT and GRN mutations can be found in clinical series of AD most likely due to misdiagnosis. This study clearly demonstrates that rare variants in these genes could explain an important proportion of genetic heritability of AD, which is not detected by GWAS

The high energy muon spectrum in Extensive Air Showers: first data from LVD and EAS-TOP at Gran Sasso

We present evidence for a dependence of the average deep underground muon energies on shower size in the coincident EAS-TOP and LVD data at the Gran Sasso laboratories. The measured relation agrees with a mixed chemical composition of the cosmic ray primary spectrum at energies around 10(15) eV. (C) 1998 Elsevier Science B.V.9318519

SINGLE MUONS IN THE LARGE-VOLUME DETECTOR

The first angular distribution data from 5547 hours of operation of the LVD detector are presented. A total of 452,630 single muons were reconstructed for this period. We present, for the first time from Gran Sasso Laboratory, data at near-horizontal zenith angles.3524024

MULTIPLE MUON EVENTS OBSERVED IN THE LVD EXPERIMENT

This is a progress report on the multiple muon events recorded by the first tower of the LVD detector at the Gran Sasso Laboratory. About 17,000 multiple muon events have been observed since the LVD first tower started operation in June 1992. Presented here are the measured multiplicity distribution and separation distribution of muon pairs in the bundles.3524324

SEARCH FOR NEUTRINOS FROM COLLAPSING STARS WITH THE LVD AT GRAN-SASSO

The Large Volume Detector (LVD) in the Gran Sasso underground Laboratory is a multipurpose detector consisting of a large volume of liquid scintillator interleaved with limited streamer tubes. In this paper we discuss its power to study low energy cosmic neutrinos. The results show that the first of the five LVD towers, operational since June 1992 with 368 tons of liquid scintillator, is well suited to detect neutrinos from collapsing stars within all our Galaxy, over a wide range of burst duration (up to a few hundreds seconds). One year data, collected since June 1992, have been analized and results are here discussed. No evidence for burst candidates has been found in this period of data taking.3526726