GSE5281 Human Brain Alzheimer Full Liang (Jul09) RMAmodify this page

Accession number: GN313

Please cite: Liang WS, Reiman EM, Valla J, Dunckley T, Beach TG, Grover A, Niedzielko TL, Schneider LE, Mastroeni D, Caselli R, Kukull W, Morris JC, Hulette CM, Schmechel D, Rogers J, Stephan DA (2008) Alzheimer's disease is associated with reduced expression of energy metabolism genes in posterior cingulate neurons. Proc Natl Acad Sci USA 105:4441-4446.

Human brain expression data in patients with Alzheimer's disease and age-matched elderly control subjects. This cortical expression data set is taken from GEO GSE5281 (Liang et al. 2006, Liang et al. 2008). Samples were laser-captured from cortical regions of 16 normal elderly humans (10 males and 4 females) and from 33 AD cases (15 males and 18 females). Mean age of cases and controls was 80 years. All samples were run on the Affymetrix U133 Plus 2.0 array. We renormalized the RMA data to an average expression of 8 units on a log2 scale. Two versions of the data have been entered in GeneNetwork: one consisting of 157 of 161 arrays (full set minus 4 arrays we consider of poor quality); the second consisting of what we regard as the best 102 arrays (those with mean correlations of better than 0.88 with all other arrays). Case IDs have the following code structure: Brain Region, GEO ID, Sex, Age, Disease Status. E119615M63N is a sample of the entorhinal cortex of case GSM119615, a male 63 year old normal case. The tissue codes are E = enorhinal cortex layer II, H = hippocampus CA1 pyramidal layer, MT = medial temporal cortex layer III, PC = porterior cingulate cortex layer III, SP = supeior frontal cortex layer III, V = primary visual cortex area 17 layer III. GeneNetwork does not yet allow sophisticated display of the data, but you can perform correlation analyses of any of the 56,000 probe sets. For example, expression of the APP transcript is higher in the AD cases and correlates well with many other AD related genes.

NOTE: We detected a minimum of 7.6% case assignment error rate (12 of 158 arrays) in this data set. Twelve cases are assigned to the wrong sex (see XIST probe set 224588_at, the figure below, and table 1). This raises the possibility that some cases are also misassigned by cortical brain region and disease status.

Legend: Expression of the sex-specific gene XIST reveals about 10 sex assignment errors in this data set.

Samples were laser-captured from cortical layer 3 (except the hippocampus) and run on the Affymetrix U133 Plus 2.0 array. We renormalized the data to an average expression of 8 units on a log2 scale. Case IDs have the following code structure: Brain Region, GEO ID, Sex, Age, Disease Status. E119615M63N is a sample of the entorhinal cortex of case GSM119615, a male 63 year old normal case. The tissue codes are E = enorhinal cortex layer II, H = hippocampus CA1 pyramidal layer, MT = medial temporal cortex layer III, PC = porterior cingulate cortex layer III, SP = supeior frontal cortex layer III, V = primary visual cortex layer III. A total of 16 normal subjects were used (10 M and 4 female). The AD samples

. GeneNetwork does not allow sophisticated display of the data, but you can perform correlation analyses of any of the 56,000 probe sets. For example expression of the APP transcript is higher in the AD cases and correlates well with many other AD related genes.

Summary: (Taken verbatim from the GEO record)

Information about the genes that are preferentially expressed during the course of Alzheimer’s disease (AD) could improve our understanding of the molecular mechanisms involved in the pathogenesis of this common cause of cognitive impairment in older persons, provide new opportunities in the diagnosis, early detection, and tracking of this disorder, and provide novel targets for the discovery of interventions to treat and prevent this disorder. Information about the genes that are preferentially expressed in relationship to normal neurological aging could provide new information about the molecular mechanisms that are involved in normal age-related cognitive decline and a host of age-related neurological disorders, and they could provide novel targets for the discovery of interventions to mitigate some of these deleterious effects.

Aim 1. Collect brain samples from three Alzheimer’s Disease Centers (ADCs) for subsequent gene expression profiling. Individuals will be stratified with respect to diagnostic groups (using both clinical and neuropathological criteria), age groups, and APOE genotype. 150 individual brains will be sampled from the Arizona ADC, the Duke University ADC, and the Washington University ADC. Miniscule sample sizes (200 um of sectioned tissue) from six brain regions that are histopathologically or metabolically relevant to AD and aging will be collected, ensuring that this proposal does not deplete the national resource. Frozen and fixed samples will be sent to Phoenix, sectioned in a standardized fashion, and then returned. Aim 2. Tissue heterogeneity will be eliminated prior to expression profiling by performing laser capture microscopy on all brain regions. Aim 3. Expression profile LCM-captured cells on the Affymetrix U133 Plus 2.0 array (~55,000 transcripts), and quickly provide these data to the community at large. Aim 4. Identify pathogenic cascades related to each of the clinico-pathologic correlates using unsupervised and supervised analyses coupled with a hypothesis-driven approach. Aim 5. Validation of the expression correlates at the protein and functional levels.

Scientific progress in the last few years has improved our understanding of AD and raised the hope of identifying treatments to halt the progression and prevent the onset of this disorder. For instance, researchers have begun to characterize the cascade of molecular events which lead to the major histopathological features of the disorder: neuritic plaques, which contain extra-cellular deposits of amyloid beta-peptides (Abeta); neurofibrillary tangles, which contain the hyperphosphorylated form of the intracellular, microtubule-associated protein, tau; and a loss of neurons and synapses. These molecular events provide targets for the development of promising new treatments. For example, A-beta has been postulated to trigger a cascade of events that are involved in the pathogenesis of AD. This proposal hopes to provide new information about the genes that are preferentially expressed in the development of AD histopathology, including the over-expression of APP, amyloid-induced neurotoxicity, and hyperphosphorylation of tau, as well as bring clarity to the metabolic abnormalities that seem to play a role in dementia and AD development and pathology.

We will perform LCM on 6 brain regions with about 14 biological replicates per brain region. The brain regions are as follows: 1) entorhinal cortex 2) hippocampus 3) medial temporal gyrus 4) posterior cingulate 5) superior frontal gyrus and 6) primary visual cortex. We will collect layer III pyramidal cells from the white matter in each region, isolate total RNA from LCMed cell lysates, and perform double round amplification of each sample for array analysis.

Bad arrays excluded: Four samples, highlighted in the table below, are bad arrays. For quality control, they should be excluded.

IndexGEO SeriesOrgan RegionTissueCase IDAgeSex
1GSM119615Entorhinal CortexNormalE119615M63N63M
2GSM119616Entorhinal CortexNormalE119616M85N85M
3GSM119617Entorhinal CortexNormalE119617M80N80M
4GSM119618Entorhinal CortexNormalE119618M->F80N80M
5GSM119619Entorhinal CortexNormalE119619F->M102N102F
6GSM119620Entorhinal CortexNormalE119620M79N79M
7GSM119621Entorhinal CortexNormalE119621M76N76M
8GSM119622Entorhinal CortexNormalE119622M83N83M
9GSM119623Entorhinal CortexNormalE119623M79N79M
10GSM119624Entorhinal CortexNormalE119624F88N88F
11GSM119625Entorhinal CortexNormalE119625F82N82F
12GSM119626Entorhinal CortexNormalE119626M69N69M
13GSM119627Entorhinal CortexNormalE119627M78N78M
14GSM238763Entorhinal CortexAlzheimer'sE238763F82A82F
15GSM238790Entorhinal CortexAlzheimer'sE238790F86A86F
16GSM238791Entorhinal CortexAlzheimer'sE238791F93A93F
17GSM238792Entorhinal CortexAlzheimer'sE238792M84A84M
18GSM238793Entorhinal CortexAlzheimer'sE238793F79A79F
19GSM238794Entorhinal CortexAlzheimer'sE238794F78A78F
20GSM238795Entorhinal CortexAlzheimer'sE238795F91A91F
21GSM238796Entorhinal CortexAlzheimer'sE238796M86A86M
22GSM238797Entorhinal CortexAlzheimer'sE238797NA0AN/AN/A
23GSM238798Entorhinal CortexAlzheimer'sE238798M80A80M
24GSM119628HippocampusNormalH119628M85N85M
25GSM119629HippocampusNormalH119629M80N80M
26GSM119630HippocampusNormalH119630M80N80M
27GSM119631HippocampusNormalH119631F102N102F
28GSM119632HippocampusNormalH119632M63N63M
29GSM119633HippocampusNormalH119633M79N79M
30GSM119634HippocampusNormalH119634M76N76M
31GSM119635HippocampusNormalH119635M83N83M
32GSM119636HippocampusNormalH119636M79N79M
33GSM119637HippocampusNormalH119637F88N88F
34GSM119638HippocampusNormalH119638F73N73F
35GSM119639HippocampusNormalH119639M69N69M
36GSM119640HippocampusNormalH119640M78N78M
37GSM238799HippocampusAlzheimer'sH238799F73A73F
38GSM238800HippocampusAlzheimer'sH238800M81A81M
39GSM238801HippocampusAlzheimer'sH238801M78A78M
40GSM238802HippocampusAlzheimer'sH238802M75A75M
41GSM238803HippocampusAlzheimer'sH238803F70A70F
42GSM238804HippocampusAlzheimer'sH238804F85A85F
43GSM238805HippocampusAlzheimer'sH238805F77A77F
44GSM238806HippocampusAlzheimer'sH238806M79A79M
45GSM238807HippocampusAlzheimer'sH238807M88A88M
46GSM238808HippocampusAlzheimer'sH238808M72A72M
47GSM119641Medial Temporal GyrusNormalMT119641M85N85M
48GSM119642Medial Temporal GyrusNormalMT119642M80N80M
49GSM119643Medial Temporal GyrusNormalMT119643F102N102F
50GSM119644Medial Temporal GyrusNormalMT119644M63N63M
51GSM119645Medial Temporal GyrusNormalMT119645M79N79M
52GSM119646Medial Temporal GyrusNormalMT119646M83N83M
53GSM119647Medial Temporal GyrusNormalMT119647M79N79M
54GSM119648Medial Temporal GyrusNormalMT119648F88N88F
55GSM119649Medial Temporal GyrusNormalMT119649F82N82F
56GSM119650Medial Temporal GyrusNormalMT119650F73N73F
57GSM119651Medial Temporal GyrusNormalMT119651M69N69M
58GSM119652Medial Temporal GyrusNormalMT119652M->F78N78M
59GSM238809Medial Temporal GyrusAlzheimer'sMT238809M81A81M
60GSM238810Medial Temporal GyrusAlzheimer'sMT238810M72A72M
61GSM238811Medial Temporal GyrusAlzheimer'sMT238811M75A75M
62GSM238812Medial Temporal GyrusAlzheimer'sMT238812M78A78M
63GSM238813Medial Temporal GyrusAlzheimer'sMT238813M75A75M
64GSM238815Medial Temporal GyrusAlzheimer'sMT238815F95A95F
65GSM238816Medial Temporal GyrusAlzheimer'sMT238816F81A81F
66GSM238817Medial Temporal GyrusAlzheimer'sMT238817F85A85F
67GSM238818Medial Temporal GyrusAlzheimer'sMT238818M79A79M
68GSM238819Medial Temporal GyrusAlzheimer'sMT238819F82A82F
69GSM238820Medial Temporal GyrusAlzheimer'sMT238820M88A88M
70GSM238821Medial Temporal GyrusAlzheimer'sMT238821M72A72M
71GSM238822Medial Temporal GyrusAlzheimer'sMT238822F73A73F
72GSM238823Medial Temporal GyrusAlzheimer'sMT238823M87A87M
73GSM238824Medial Temporal GyrusAlzheimer'sMT238824M68A68M
74GSM238825Medial Temporal GyrusAlzheimer'sMT238825F80A80F
75GSM119653Posterior CingulateNormalPC119653M85N85M
76GSM119654Posterior CingulateNormalPC119654M80N80M
77GSM119655Posterior CingulateNormalPC119655F102N102F
78GSM119656Posterior CingulateNormalPC119656M63N63M
79GSM119657Posterior CingulateNormalPC119657M79N79M
80GSM119658Posterior CingulateNormalPC119658M->F76N76M
81GSM119659Posterior CingulateNormalPC119659M83N83M
82GSM119660Posterior CingulateNormalPC119660M79N79M
83GSM119661Posterior CingulateNormalPC119661F88N88F
84GSM119662Posterior CingulateNormalPC119662F82N82F
85GSM119663Posterior CingulateNormalPC119663F73N73F
86GSM119664Posterior CingulateNormalPC119664M69N69M
87GSM119665Posterior CingulateNormalPC119665M78N78M
88GSM238826Posterior CingulateAlzheimer'sPC238826F73A73F
89GSM238827Posterior CingulateAlzheimer'sPC238827M81A81M
90GSM238834Posterior CingulateAlzheimer'sPC238834M78A78M
91GSM238835Posterior CingulateAlzheimer'sPC238835M75A75M
92GSM238837Posterior CingulateAlzheimer'sPC238837M68A68M
93GSM238838Posterior CingulateAlzheimer'sPC238838F70A70F
94GSM238839Posterior CingulateAlzheimer'sPC238839F85A85F
95GSM238840Posterior CingulateAlzheimer'sPC238840M79A79M
96GSM238841Posterior CingulateAlzheimer'sPC238841M88A88M
97GSM119666Superior Frontal GyrusNormalSF119666M79N79M
98GSM119667Superior Frontal GyrusNormalSF119667F->M88N88F
99GSM119668Superior Frontal GyrusNormalSF119668F->M82N82F
100GSM119669Superior Frontal GyrusNormalSF119669F->M73N73F
101GSM119670Superior Frontal GyrusNormalSF119670F->M102N102F
102GSM119671Superior Frontal GyrusNormalSF119671M63N63M
103GSM119672Superior Frontal GyrusNormalSF119672M->F79N79M
104GSM119673Superior Frontal GyrusNormalSF119673M->F76N76M
105GSM119674Superior Frontal GyrusNormalSF119674M->F83N83M
106GSM119675Superior Frontal GyrusNormalSF119675M69N69M
107GSM119676Superior Frontal GyrusNormalSF119676M78N78M
108GSM238842Superior Frontal GyrusAlzheimer'sSF238842F73A73F
109GSM238843Superior Frontal GyrusAlzheimer'sSF238843M81A81M
110GSM238844Superior Frontal GyrusAlzheimer'sSF238844M72A72M
111GSM238845Superior Frontal GyrusAlzheimer'sSF238845M75A75M
112GSM238846Superior Frontal GyrusAlzheimer'sSF238846M78A78M
113GSM238847Superior Frontal GyrusAlzheimer'sSF238847M75A75M
114GSM238848Superior Frontal GyrusAlzheimer'sSF238848M87A87M
115GSM238851Superior Frontal GyrusAlzheimer'sSF238851F95A95F
116GSM238854Superior Frontal GyrusAlzheimer'sSF238854M68A68M
117GSM238855Superior Frontal GyrusAlzheimer'sSF238855F95A95F
118GSM238856Superior Frontal GyrusAlzheimer'sSF238856F70A70F
119GSM238857Superior Frontal GyrusAlzheimer'sSF238857F85A85F
120GSM238858Superior Frontal GyrusAlzheimer'sSF238858F83A83F
121GSM238860Superior Frontal GyrusAlzheimer'sSF238860F77A77F
122GSM238861Superior Frontal GyrusAlzheimer'sSF238861F83A83F
123GSM238862Superior Frontal GyrusAlzheimer'sSF238862M68A68M
124GSM238863Superior Frontal GyrusAlzheimer'sSF238863M79A79M
125GSM238864Superior Frontal GyrusAlzheimer'sSF238864F82A82F
126GSM238865Superior Frontal GyrusAlzheimer'sSF238865M88A88M
127GSM238867Superior Frontal GyrusAlzheimer'sSF238867F80A80F
128GSM238868Superior Frontal GyrusAlzheimer'sSF238868M74A74M
129GSM238870Superior Frontal GyrusAlzheimer'sSF238870M72A72M
130GSM238871Superior Frontal GyrusAlzheimer'sSF238871M80A80M
131GSM119677Primary Visual CortexNormalV119677M85N85M
132GSM119678Primary Visual CortexNormalV119678M80N80M
133GSM119679Primary Visual CortexNormalV119679M63N63M
134GSM119680Primary Visual CortexNormalV119680M79N79M
135GSM119681Primary Visual CortexNormalV119681M76N76M
136GSM119682Primary Visual CortexNormalV119682M83N83M
137GSM119683Primary Visual CortexNormalV119683M79N79M
138GSM119684Primary Visual CortexNormalV119684F88N88F
139GSM119685Primary Visual CortexNormalV119685F82N82F
140GSM119686Primary Visual CortexNormalV119686F73N73F
141GSM119687Primary Visual CortexNormalV119687M69N69M
142GSM119688Primary Visual CortexNormalV119688M78N78M
143GSM238872Primary Visual CortexAlzheimer'sV238872F73A73F
144GSM238873Primary Visual CortexAlzheimer'sV238873M81A81M
145GSM238874Primary Visual CortexAlzheimer'sV238874M75A75M
146GSM238875Primary Visual CortexAlzheimer'sV238875M78A78M
147GSM238877Primary Visual CortexAlzheimer'sV238877M75A75M
148GSM238941Primary Visual CortexAlzheimer'sV238941M87A87M
149GSM238942Primary Visual CortexAlzheimer'sV238942F95A95F
150GSM238943Primary Visual CortexAlzheimer'sV238943M68A68M
151GSM238944Primary Visual CortexAlzheimer'sV238944F70A70F
152GSM238945Primary Visual CortexAlzheimer'sV238945F81A81F
153GSM238946Primary Visual CortexAlzheimer'sV238946F85A85F
154GSM238947Primary Visual CortexAlzheimer'sV238947M68A68M
155GSM238948Primary Visual CortexAlzheimer'sV238948M79A79M
156GSM238949Primary Visual CortexAlzheimer'sV238949F82A82F
157GSM238951Primary Visual CortexAlzheimer'sV238951M88A88M
158GSM238952Primary Visual CortexAlzheimer'sV238952M74A74M
159GSM238953Primary Visual CortexAlzheimer'sV238953M72A72M
160GSM238955Primary Visual CortexAlzheimer'sV238955M->F68A68M
161GSM238963Primary Visual CortexAlzheimer'sV238963F80A80F

Web Link:

http://arrayconsortium.tgen.org/np2/viewProject.do?action=viewProject&projectId=433773

Citations:

Liang WS, Dunckley T, Beach TG, Grover A et al. Gene expression profiles in anatomically and functionally distinct regions of the normal aged human brain. Physiol Genomics 2007 Feb 12;28(3):311-22. PMID: 17077275
Liang WS, Reiman EM, Valla J, Dunckley T et al. Alzheimer's disease is associated with reduced expression of energy metabolism genes in posterior cingulate neurons. Proc Natl Acad Sci U S A 2008 Mar 18;105(11):4441-6. PMID: 18332434