Mutation Analysis of Sporadic Early-Onset Alzheimer’s Disease using the NeuroX Array

Imelda S. Barber; Anne Braae; Naomi Clement; Tulsi Patel; Tamar Guetta-Baranes; Keeley Brookes; Christopher Medway; Sally Chappell; Rita Guerreiro; Jose Bras; Dena Hernandez; Andrew Singleton; John Hardy; David M. Mann; Peter Passmore; David Craig; Janet Johnston; Bernadette McGuinness; Stephen Todd; Reinhard Heun; Heike Kölsch; Patrick G. Kehoe; Emma R.L.C. Vardy; Nigel M. Hooper; Stuart Pickering-Brown; Julie Snowden; Anna Richardson; Matthew Jones; David Neary; Jennifer Harris; James Lowe; A. David Smith; Gordon K Wilcock; Donald Warden; Clive Holmes; Kevin Morgan

doi:10.1016/j.neurobiolaging.2016.09.008

Mutation Analysis of Sporadic Early-Onset Alzheimer’s Disease using the NeuroX Array

Imelda S. Barber, Anne Braae, Naomi Clement, Tulsi Patel, Tamar Guetta-Baranes, Keeley Brookes, Christopher Medway, Sally Chappell, Rita Guerreiro, Jose Bras, Dena Hernandez, Andrew Singleton, John Hardy, David M. Mann, Peter Passmore, David Craig, Janet Johnston, Bernadette McGuinness, Stephen Todd, Reinhard HeunHeike Kölsch, Patrick G. Kehoe, Emma R.L.C. Vardy, Nigel M. Hooper, Stuart Pickering-Brown, Julie Snowden, Anna Richardson, Matthew Jones, David Neary, Jennifer Harris, James Lowe, A. David Smith, Gordon K Wilcock, Donald Warden, Clive Holmes, Kevin Morgan

Research output: Contribution to journal › Article (Academic Journal) › peer-review

23 Citations (Scopus)

503 Downloads (Pure)

Abstract

We have screened sporadic early-onset Alzheimer’s disease (sEOAD, n=408) samples using the NeuroX array for known causative and predicted pathogenic variants in 16 genes linked to familial forms of neurodegeneration. We found two sEOAD individuals harbouring a known causative variant in PARK2 known to cause early-onset Parkinson’s disease (EOPD); p.T240M (n=1) and p.Q34fs delAG (n=1). Additionally, we identified three sEOAD individuals harbouring a predicted pathogenic variant in MAPT (p.A469T) which has previously been associated with AD. It is currently unknown if these variants affect susceptibility to sEOAD, further studies would be needed to establish this. This work highlights the need to screen sEOAD individuals for variants that are more classically attributed to other forms of neurodegeneration.

Original language	English
Pages (from-to)	215.e1-215.e8
Number of pages	8
Journal	Neurobiology of Aging
Volume	49
Early online date	23 Sept 2016
DOIs	https://doi.org/10.1016/j.neurobiolaging.2016.09.008
Publication status	Published - Jan 2017

Research Groups and Themes

Cerebrovascular and Dementia Research Group

Keywords

Alzheimer’s disease
Parkinson’s disease
sporadic
early-onset
NeuroX
screening

Access to Document

10.1016/j.neurobiolaging.2016.09.008

Full-text PDF (accepted author manuscript)
This is the accepted author manuscript (AAM). The final published version (version of record) is available online via Elsevier at http://dx.doi.org/10.1016/j.neurobiolaging.2016.09.008. Please refer to any applicable terms of use of the publisher.
Accepted author manuscript, 694 KBLicence: CC BY-NC-ND
Supplementary information PDFOther version, 460 KB

Handle.net

Persistent link

Cite this

Barber, I. S., Braae, A., Clement, N., Patel, T., Guetta-Baranes, T., Brookes, K., Medway, C., Chappell, S., Guerreiro, R., Bras, J., Hernandez, D., Singleton, A., Hardy, J., Mann, D. M., Passmore, P., Craig, D., Johnston, J., McGuinness, B., Todd, S., ... Morgan, K. (2017). Mutation Analysis of Sporadic Early-Onset Alzheimer’s Disease using the NeuroX Array. Neurobiology of Aging, 49, 215.e1-215.e8. https://doi.org/10.1016/j.neurobiolaging.2016.09.008

@article{36c33115a3bc40fbac3ec5569a54eb91,

title = "Mutation Analysis of Sporadic Early-Onset Alzheimer{\textquoteright}s Disease using the NeuroX Array",

abstract = "We have screened sporadic early-onset Alzheimer{\textquoteright}s disease (sEOAD, n=408) samples using the NeuroX array for known causative and predicted pathogenic variants in 16 genes linked to familial forms of neurodegeneration. We found two sEOAD individuals harbouring a known causative variant in PARK2 known to cause early-onset Parkinson{\textquoteright}s disease (EOPD); p.T240M (n=1) and p.Q34fs delAG (n=1). Additionally, we identified three sEOAD individuals harbouring a predicted pathogenic variant in MAPT (p.A469T) which has previously been associated with AD. It is currently unknown if these variants affect susceptibility to sEOAD, further studies would be needed to establish this. This work highlights the need to screen sEOAD individuals for variants that are more classically attributed to other forms of neurodegeneration.",

keywords = "Alzheimer{\textquoteright}s disease, Parkinson{\textquoteright}s disease, sporadic, early-onset, NeuroX, screening",

author = "Barber, {Imelda S.} and Anne Braae and Naomi Clement and Tulsi Patel and Tamar Guetta-Baranes and Keeley Brookes and Christopher Medway and Sally Chappell and Rita Guerreiro and Jose Bras and Dena Hernandez and Andrew Singleton and John Hardy and Mann, {David M.} and Peter Passmore and David Craig and Janet Johnston and Bernadette McGuinness and Stephen Todd and Reinhard Heun and Heike K{\"o}lsch and Kehoe, {Patrick G.} and Vardy, {Emma R.L.C.} and Hooper, {Nigel M.} and Stuart Pickering-Brown and Julie Snowden and Anna Richardson and Matthew Jones and David Neary and Jennifer Harris and James Lowe and Smith, {A. David} and Wilcock, {Gordon K} and Donald Warden and Clive Holmes and Kevin Morgan",

year = "2017",

month = jan,

doi = "10.1016/j.neurobiolaging.2016.09.008",

language = "English",

volume = "49",

pages = "215.e1--215.e8",

journal = "Neurobiology of Aging",

issn = "0197-4580",

publisher = "Elsevier Inc.",

}

Barber, IS, Braae, A, Clement, N, Patel, T, Guetta-Baranes, T, Brookes, K, Medway, C, Chappell, S, Guerreiro, R, Bras, J, Hernandez, D, Singleton, A, Hardy, J, Mann, DM, Passmore, P, Craig, D, Johnston, J, McGuinness, B, Todd, S, Heun, R, Kölsch, H, Kehoe, PG, Vardy, ERLC, Hooper, NM, Pickering-Brown, S, Snowden, J, Richardson, A, Jones, M, Neary, D, Harris, J, Lowe, J, Smith, AD, Wilcock, GK, Warden, D, Holmes, C & Morgan, K 2017, 'Mutation Analysis of Sporadic Early-Onset Alzheimer’s Disease using the NeuroX Array', Neurobiology of Aging, vol. 49, pp. 215.e1-215.e8. https://doi.org/10.1016/j.neurobiolaging.2016.09.008

TY - JOUR

T1 - Mutation Analysis of Sporadic Early-Onset Alzheimer’s Disease using the NeuroX Array

AU - Barber, Imelda S.

AU - Braae, Anne

AU - Clement, Naomi

AU - Patel, Tulsi

AU - Guetta-Baranes, Tamar

AU - Brookes, Keeley

AU - Medway, Christopher

AU - Chappell, Sally

AU - Guerreiro, Rita

AU - Bras, Jose

AU - Hernandez, Dena

AU - Singleton, Andrew

AU - Hardy, John

AU - Mann, David M.

AU - Passmore, Peter

AU - Craig, David

AU - Johnston, Janet

AU - McGuinness, Bernadette

AU - Todd, Stephen

AU - Heun, Reinhard

AU - Kölsch, Heike

AU - Kehoe, Patrick G.

AU - Vardy, Emma R.L.C.

AU - Hooper, Nigel M.

AU - Pickering-Brown, Stuart

AU - Snowden, Julie

AU - Richardson, Anna

AU - Jones, Matthew

AU - Neary, David

AU - Harris, Jennifer

AU - Lowe, James

AU - Smith, A. David

AU - Wilcock, Gordon K

AU - Warden, Donald

AU - Holmes, Clive

AU - Morgan, Kevin

PY - 2017/1

Y1 - 2017/1

N2 - We have screened sporadic early-onset Alzheimer’s disease (sEOAD, n=408) samples using the NeuroX array for known causative and predicted pathogenic variants in 16 genes linked to familial forms of neurodegeneration. We found two sEOAD individuals harbouring a known causative variant in PARK2 known to cause early-onset Parkinson’s disease (EOPD); p.T240M (n=1) and p.Q34fs delAG (n=1). Additionally, we identified three sEOAD individuals harbouring a predicted pathogenic variant in MAPT (p.A469T) which has previously been associated with AD. It is currently unknown if these variants affect susceptibility to sEOAD, further studies would be needed to establish this. This work highlights the need to screen sEOAD individuals for variants that are more classically attributed to other forms of neurodegeneration.

AB - We have screened sporadic early-onset Alzheimer’s disease (sEOAD, n=408) samples using the NeuroX array for known causative and predicted pathogenic variants in 16 genes linked to familial forms of neurodegeneration. We found two sEOAD individuals harbouring a known causative variant in PARK2 known to cause early-onset Parkinson’s disease (EOPD); p.T240M (n=1) and p.Q34fs delAG (n=1). Additionally, we identified three sEOAD individuals harbouring a predicted pathogenic variant in MAPT (p.A469T) which has previously been associated with AD. It is currently unknown if these variants affect susceptibility to sEOAD, further studies would be needed to establish this. This work highlights the need to screen sEOAD individuals for variants that are more classically attributed to other forms of neurodegeneration.

KW - Alzheimer’s disease

KW - Parkinson’s disease

KW - sporadic

KW - early-onset

KW - NeuroX

KW - screening

U2 - 10.1016/j.neurobiolaging.2016.09.008

DO - 10.1016/j.neurobiolaging.2016.09.008

M3 - Article (Academic Journal)

C2 - 27776828

SN - 0197-4580

VL - 49

SP - 215.e1-215.e8

JO - Neurobiology of Aging

JF - Neurobiology of Aging

ER -

Mutation Analysis of Sporadic Early-Onset Alzheimer’s Disease using the NeuroX Array

Abstract

Research Groups and Themes

Keywords

Access to Document

Handle.net

Fingerprint

Cite this