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Research on Familial forms of Dementia
By carefully studying families with a number
of first degree relatives with dementia, Professor
Halliday and her colleagues have found that these families
often have unique clinical and pathological features. They
have also found that by analysing the biological basis for
these differences, they can identify important pathways that
may be amenable to new forms of treatments. Professor Halliday’s
ongoing studies are identifying the differences in the proteins
involved and how these proteins interact to cause the different
pathologies often seen in familial dementias. We believe this
work will identify better molecules to target for therapeutic
treatments.
Dr
Brooks records details of the family history and the
clinical features of the condition in affected family members.
Key individuals are then invited to give a blood sample for
DNA studies which are currently carried out by colleagues at the Garvan Institute for Medical
Research. Currently funded projects include a study to
determine genes that modify the normal disease process in
Alzheimer's disease and frontotemporal dementia. In another
project we are starting to analyse whether there is a genetic
basis to dementia with Lewy bodies in families that either
have the symptoms of this disease or autopsy confirmation in
their family. Because of their inheritance patterns, we are
expecting that these families will also have single gene
mutations and/or deletions. Our hypothesis is that the genetic
basis of familial dementia with Lewy bodies will differ from
that of familial Alzheimer's disease.
How can I help this research?
By participating in our DNA
donation and brain
donor programs. People with a
family history of dementia in several members, particularly if
symptoms have developed before 60 years of age, could ring Dr
Brooks on 9399 1101. We need both affected
and unaffected family members to undergo a detailed medical
examination and to provide a sample of blood for DNA analysis.
Blood will also be prepared for immortalisation of lymphocytes.
Key researchers
Peter Schofield, William
Brooks, Tony
Broe, Glenda
Halliday, Claire
Shepherd and Yue Huang
Collaborators
John
Kwok (Garvan Institute)
Key publications
Piguet O, Brooks WS, Halliday G, Schofield
PR, Stanford PM, Kwok J, Spillantini MG, Yankopoulou D, Nestor
PJ, Broe GA, Hodges JR (2004) Similar early clinical
presentations in familial and non-familial frontotemporal
dementia, Journal of Neurology, Neurosurgery and Psychiatry
75:1743-1745
Stanford PM, Brooks WS, Teber ET, Hallup M, McLean C,
Halliday GM, Martins RN, Kwok JBJ, Schofield PR (2004)
Frequency of tau mutations in familial and sporadic
frontotemporal dementia and other tauopathies, Journal of
Neurology 251:1098-1104
Kwok JBJ, Halliday GM, Brooks WS, Dolios G, Laudon H, Murayama
O, Hallup M, Badenhop RF, Vickers J, Wang R, Naslund J, Gandy
SE, Takashima A, Schofield PR (2003). Presenilin-1 mutation
(leu271val) results in altered exon 8 splicing and Alzheimer's
disease with non-cored plaques and no neuritic dystrophy.
Journal of Biological Chemistry; 278:6748-6754.
Brooks WS, Kwok JBJ, Halliday GM, Godbolt A, Rossor MN,
Creasey H, Jones AO, Schofield PR (2004) Hemorrhage is
uncommon in a new Alzheimer's family with the Flemish amyloid
precursor protein mutation, Neurology 63:1613-1617
Shepherd CS, Gregory GC, Vickers JC, Brooks WS, Kwok JBJ,
Schofield PR, Kril JJ, Halliday GM (2004) Positional effects
of presenilin-1 mutations on tau phosphorylation in cortical
plaques, Neurobiology of Disease 15:115-119
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