Poster Presentations: P4 P677

previously reported cases. Methods: The MAP-T R406W mutation was

identified via whole-exome sequencing (Agilent SureSelect). Affected

members were then comprehensively re-evaluated with neurological and

neuropsychological exams. A review of medical and research records in-

cluded serial physical, neurological, and cognitive examinations, clinical

history from family members, and imaging results. Results: All tested,

affected family members carried the R406W mutation. Clinical data was

available on five of the six affected family members. Each presented with

early-onset (range: 48-62 years), memory loss, with a pattern similar to

that of late-onset Alzheimer’s Disease. However, unlike most previously de-

scribed cases, four of the five individuals developed a gradual progression of

Parkinsonian symptoms. The severity of Parkinsonian symptoms paralleled

the course of dementia; the affected member without Parkinsonian symp-

toms died early in the course of illness.In the majority of previously de-

scribed cases, frontal atrophy was readily demonstrated on neuroimaging,

and frontal features were variably present in the clinical history and

exam. In this family, there was not prominent temporal atrophy in four of

the five affected members, and clinical indications of frontal dysfunction

were variable. Conclusions: The clinical presentation of the MAP-T

R406W individuals in this family differs from previously described cases

in that Parkinsonian features are associated with progression of dementia,

and imaging does not reveal prominent frontal atrophy. Clinical variability

may represent separate genetic influences on genotype.

P4-130 ASSESSMENT OF MITOCHONDRIAL DNA FROM

PERIPHERAL BLOOD OFALZHEIMER’S

PATIENTS: COPY NUMBER, DELETIONS AND

POINT MUTATIONS

Rhonda Roby, Nicole Phillips, James Simpkins, University of North Texas

Health Science Center, Ft. Worth, Texas, United States.

Background: Studies of mitochondrial function have become increas-

ingly prominent in age-related disease research, specifically, late onset

Alzheimer’s disease (loAD). Mitochondria are involved in a host of ho-

meostatic and signaling processes which extend well beyond ATP pro-

duction. These processes rely on both nuclear and mitochondrial

encoded genes. Mitochondrial malfunction has long been associated

with loAD, and alterations to the mitochondrial genome are thought to

contribute to pathogenesis; the mechanism, however, remains unclear.

We hypothesize that loAD is the result of systemic mitochondrial mal-

function that occurs with advancing age but manifests specifically in

the brain due to the highly energetic nature of this organ. Consequently,

mitochondrial DNA (mtDNA)in the peripheral blood also accumulates

damage at an increased rate as compared to age-matched normal con-

trols; this accumulation can serve as a marker for the early stages of dis-

ease progression. Methods: In this study, we tested this hypothesis using

repository samples from the Texas Alzheimer’s Research and Care Con-

sortium (TARCC). TARCC longitudinally (annually) collects data (i.e.,

neuropsychological testing, medically-related risk factors) and peripheral

blood from loAD patients, mild cognitive impairment (MCI) patients, and

normal controls (NC). Extracted mtDNA samples from the peripheral

blood (mtDNA PB) of 100 loAD patients and 100 NC subjects were tested

for group differences in three measures of mtDNA integrity. MtDNA PB

were screened for point mutations using a high throughput mass spectrom-

etry tiling assay which covers the mtDNA control region; direct sequenc-

ing was performed to confirm the specific mutation base position(s).

MtDNA PB copy number was assessed by targeting two mtDNA loci

and one nuclear DNA (nDNA) locus in a real-time quantitative PCR mul-

tiplex assay. The mtDNA: nDNA ratio provides an estimate of mtDNA

copies per cell. MtDNA PB was nonspecifically screened for deletions

using a real-time qPCR assay and a long-range PCR approach. Direct

sequencing was performed to identify and characterize the regions of de-

letions. Results: The number, distribution, and group differences for NC

and loAD of point mutations, the mtDNA: nDNA ratio for copy number,

and deletions will be presented. Conclusions: Mitochondrial point

mutations, mtDNA: nDNA ratio for copy number, and deletions may be

important in LOAD.

P4-131 ASSOCIATION OF MATERNAL FAMILY HISTORY

OF DEMENTIAWITH ALZHEIMER’S DISEASE

BIOMARKERS

Robyn Honea1, Eric Vidoni2, Russell Swerdlow3, Jeffrey Burns1,1University of Kansas School of Medicine, Fairway, Kansas, United States;2University of Kansas School of Medicine, Kansas City, Kansas, United

States; 3University of Kansas, Kansas City, Kansas, United States.

Background: A family history of Alzheimer’s disease (AD) increases

one’s risk of developing late-onset Alzheimer’s Disease (LOAD), and

a maternal family history of LOAD influences risk more than a paternal

family history. Accumulating evidence suggests that a family history of

dementia associates with AD-typical biomarker changes. Methods: We

analyzed cross-sectional data from non-demented (ND), mild cognitive

impairment (MCI), and LOAD participants in the Alzheimer’s Disease

Neuroimaging Initiative (ADNI) with PET imaging using Pittsburgh Com-

pound B (PiB, n ¼ 99) and CSF analysis (n ¼ 403) for b-amyloid peptide

(Ab) and total tau. We assessed the relationship of CSF and PiB bio-

markers and family history of dementia, as well as parent gender effects.

In the larger analysis of CSF biomarkers we assessed diagnosis groups in-

dividually. A family history of dementia is associated with AD-typical bio-

marker changes. These biomarker associations are most robust in

individuals with a maternal family history, suggesting that a maternally in-

herited factor influences AD risk. Results: In the overall sample, CSFAb,

tau/Ab ratio and Global PiB uptake were significantly different between

family history positive and negative groups, with markers of increased

AD burden associated with a positive maternal family history of dementia.

Moreover, a maternal family history of dementia was associated with sig-

nificantly greater PiB b-amyloid load in the brain in the parietal cortex,

precuneus, and sensorimotor cortex. Individuals with MCI positive for

a maternal family history of dementia had significantly more markers of

AD pathophysiology than individuals with no family history of dementia.

Conclusions: A family history of dementia is associated with AD-typical

biomarker changes. These biomarker associations are most robust in

individuals with a maternal family history, suggesting that a maternally in-

herited factor influences AD risk.

P4-133 AROMATASE VARIANTS MODIFY RISK FOR

ALZHEIMER’S DISEASE IN A MULTIETHNIC

FEMALE COHORT

Sarah Janicki, Naeun Park, Rong Cheng, Nicole Schupf, Lorraine Clark,

Joseph Lee, Columbia University College of Physicians and Surgeons, New

York, New York, United States.

Background: Genetic variants that affect estrogen activity may influence

risk for Alzheimer’s disease (AD). However, most studies have been con-

ducted in Caucasian ethnic groups, and few polymorphisms have been as-

sessed in a multi-ethnic cohort in which the members have all been

evaluated in a consistent manner. Examination of polymorphisms in multi-

ethnic groups which are evaluated without taking ancestry into account may

have several limitations, including a loss of significant association due to

different allele frequencies, different linkage disequilibrium patterns be-

tween ethnicities, or differences in the distribution of comorbid conditions

and risk factors by ethnic group. We investigated the influence of CYP19

polymorphisms on risk for AD in a multiethnic cohort of women, with eth-

nicity assessed by genetic population ancestry markers (AIMs) as well as by

self-identified ethnicity. We hypothesized that genetic variants would affect

risk for AD differently in groups with different population ancestries due to

varying allele frequencies as well as disparate exposure environmental fac-

tors. Methods: 1686 women participating in the Washington Heights In-

wood Columbia Aging Project (WHICAP), were followed at 18 - 24

month intervals. Data from standardized assessments, including neurologi-

cal examination and a neuropsychological battery, were used to make an AD

diagnosis. Using multivariate logistic regression, we examined risk for AD

associated with 41 single-nucleotide polymorphisms (SNPs) on the CYP19

gene, controlling for age at time of evaluation, BMI, APOE status, current

smoking, and current or past diabetes mellitus. Results: Risk for AD was