GSE5281 Human Brain Alzheimer Full Liang (Jul09) RMA

GSE5281 Human Brain Alzheimer Full Liang (Jul09) RMA

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.

Index	GEO Series	Organ Region	Tissue	Case ID	Age	Sex
1	GSM119615	Entorhinal Cortex	Normal	E119615M63N	63	M
2	GSM119616	Entorhinal Cortex	Normal	E119616M85N	85	M
3	GSM119617	Entorhinal Cortex	Normal	E119617M80N	80	M
4	GSM119618	Entorhinal Cortex	Normal	E119618M->F80N	80	M
5	GSM119619	Entorhinal Cortex	Normal	E119619F->M102N	102	F
6	GSM119620	Entorhinal Cortex	Normal	E119620M79N	79	M
7	GSM119621	Entorhinal Cortex	Normal	E119621M76N	76	M
8	GSM119622	Entorhinal Cortex	Normal	E119622M83N	83	M
9	GSM119623	Entorhinal Cortex	Normal	E119623M79N	79	M
10	GSM119624	Entorhinal Cortex	Normal	E119624F88N	88	F
11	GSM119625	Entorhinal Cortex	Normal	E119625F82N	82	F
12	GSM119626	Entorhinal Cortex	Normal	E119626M69N	69	M
13	GSM119627	Entorhinal Cortex	Normal	E119627M78N	78	M
14	GSM238763	Entorhinal Cortex	Alzheimer's	E238763F82A	82	F
15	GSM238790	Entorhinal Cortex	Alzheimer's	E238790F86A	86	F
16	GSM238791	Entorhinal Cortex	Alzheimer's	E238791F93A	93	F
17	GSM238792	Entorhinal Cortex	Alzheimer's	E238792M84A	84	M
18	GSM238793	Entorhinal Cortex	Alzheimer's	E238793F79A	79	F
19	GSM238794	Entorhinal Cortex	Alzheimer's	E238794F78A	78	F
20	GSM238795	Entorhinal Cortex	Alzheimer's	E238795F91A	91	F
21	GSM238796	Entorhinal Cortex	Alzheimer's	E238796M86A	86	M
22	GSM238797	Entorhinal Cortex	Alzheimer's	E238797NA0A	N/A	N/A
23	GSM238798	Entorhinal Cortex	Alzheimer's	E238798M80A	80	M
24	GSM119628	Hippocampus	Normal	H119628M85N	85	M
25	GSM119629	Hippocampus	Normal	H119629M80N	80	M
26	GSM119630	Hippocampus	Normal	H119630M80N	80	M
27	GSM119631	Hippocampus	Normal	H119631F102N	102	F
28	GSM119632	Hippocampus	Normal	H119632M63N	63	M
29	GSM119633	Hippocampus	Normal	H119633M79N	79	M
30	GSM119634	Hippocampus	Normal	H119634M76N	76	M
31	GSM119635	Hippocampus	Normal	H119635M83N	83	M
32	GSM119636	Hippocampus	Normal	H119636M79N	79	M
33	GSM119637	Hippocampus	Normal	H119637F88N	88	F
34	GSM119638	Hippocampus	Normal	H119638F73N	73	F
35	GSM119639	Hippocampus	Normal	H119639M69N	69	M
36	GSM119640	Hippocampus	Normal	H119640M78N	78	M
37	GSM238799	Hippocampus	Alzheimer's	H238799F73A	73	F
38	GSM238800	Hippocampus	Alzheimer's	H238800M81A	81	M
39	GSM238801	Hippocampus	Alzheimer's	H238801M78A	78	M
40	GSM238802	Hippocampus	Alzheimer's	H238802M75A	75	M
41	GSM238803	Hippocampus	Alzheimer's	H238803F70A	70	F
42	GSM238804	Hippocampus	Alzheimer's	H238804F85A	85	F
43	GSM238805	Hippocampus	Alzheimer's	H238805F77A	77	F
44	GSM238806	Hippocampus	Alzheimer's	H238806M79A	79	M
45	GSM238807	Hippocampus	Alzheimer's	H238807M88A	88	M
46	GSM238808	Hippocampus	Alzheimer's	H238808M72A	72	M
47	GSM119641	Medial Temporal Gyrus	Normal	MT119641M85N	85	M
48	GSM119642	Medial Temporal Gyrus	Normal	MT119642M80N	80	M
49	GSM119643	Medial Temporal Gyrus	Normal	MT119643F102N	102	F
50	GSM119644	Medial Temporal Gyrus	Normal	MT119644M63N	63	M
51	GSM119645	Medial Temporal Gyrus	Normal	MT119645M79N	79	M
52	GSM119646	Medial Temporal Gyrus	Normal	MT119646M83N	83	M
53	GSM119647	Medial Temporal Gyrus	Normal	MT119647M79N	79	M
54	GSM119648	Medial Temporal Gyrus	Normal	MT119648F88N	88	F
55	GSM119649	Medial Temporal Gyrus	Normal	MT119649F82N	82	F
56	GSM119650	Medial Temporal Gyrus	Normal	MT119650F73N	73	F
57	GSM119651	Medial Temporal Gyrus	Normal	MT119651M69N	69	M
58	GSM119652	Medial Temporal Gyrus	Normal	MT119652M->F78N	78	M
59	GSM238809	Medial Temporal Gyrus	Alzheimer's	MT238809M81A	81	M
60	GSM238810	Medial Temporal Gyrus	Alzheimer's	MT238810M72A	72	M
61	GSM238811	Medial Temporal Gyrus	Alzheimer's	MT238811M75A	75	M
62	GSM238812	Medial Temporal Gyrus	Alzheimer's	MT238812M78A	78	M
63	GSM238813	Medial Temporal Gyrus	Alzheimer's	MT238813M75A	75	M
64	GSM238815	Medial Temporal Gyrus	Alzheimer's	MT238815F95A	95	F
65	GSM238816	Medial Temporal Gyrus	Alzheimer's	MT238816F81A	81	F
66	GSM238817	Medial Temporal Gyrus	Alzheimer's	MT238817F85A	85	F
67	GSM238818	Medial Temporal Gyrus	Alzheimer's	MT238818M79A	79	M
68	GSM238819	Medial Temporal Gyrus	Alzheimer's	MT238819F82A	82	F
69	GSM238820	Medial Temporal Gyrus	Alzheimer's	MT238820M88A	88	M
70	GSM238821	Medial Temporal Gyrus	Alzheimer's	MT238821M72A	72	M
71	GSM238822	Medial Temporal Gyrus	Alzheimer's	MT238822F73A	73	F
72	GSM238823	Medial Temporal Gyrus	Alzheimer's	MT238823M87A	87	M
73	GSM238824	Medial Temporal Gyrus	Alzheimer's	MT238824M68A	68	M
74	GSM238825	Medial Temporal Gyrus	Alzheimer's	MT238825F80A	80	F
75	GSM119653	Posterior Cingulate	Normal	PC119653M85N	85	M
76	GSM119654	Posterior Cingulate	Normal	PC119654M80N	80	M
77	GSM119655	Posterior Cingulate	Normal	PC119655F102N	102	F
78	GSM119656	Posterior Cingulate	Normal	PC119656M63N	63	M
79	GSM119657	Posterior Cingulate	Normal	PC119657M79N	79	M
80	GSM119658	Posterior Cingulate	Normal	PC119658M->F76N	76	M
81	GSM119659	Posterior Cingulate	Normal	PC119659M83N	83	M
82	GSM119660	Posterior Cingulate	Normal	PC119660M79N	79	M
83	GSM119661	Posterior Cingulate	Normal	PC119661F88N	88	F
84	GSM119662	Posterior Cingulate	Normal	PC119662F82N	82	F
85	GSM119663	Posterior Cingulate	Normal	PC119663F73N	73	F
86	GSM119664	Posterior Cingulate	Normal	PC119664M69N	69	M
87	GSM119665	Posterior Cingulate	Normal	PC119665M78N	78	M
88	GSM238826	Posterior Cingulate	Alzheimer's	PC238826F73A	73	F
89	GSM238827	Posterior Cingulate	Alzheimer's	PC238827M81A	81	M
90	GSM238834	Posterior Cingulate	Alzheimer's	PC238834M78A	78	M
91	GSM238835	Posterior Cingulate	Alzheimer's	PC238835M75A	75	M
92	GSM238837	Posterior Cingulate	Alzheimer's	PC238837M68A	68	M
93	GSM238838	Posterior Cingulate	Alzheimer's	PC238838F70A	70	F
94	GSM238839	Posterior Cingulate	Alzheimer's	PC238839F85A	85	F
95	GSM238840	Posterior Cingulate	Alzheimer's	PC238840M79A	79	M
96	GSM238841	Posterior Cingulate	Alzheimer's	PC238841M88A	88	M
97	GSM119666	Superior Frontal Gyrus	Normal	SF119666M79N	79	M
98	GSM119667	Superior Frontal Gyrus	Normal	SF119667F->M88N	88	F
99	GSM119668	Superior Frontal Gyrus	Normal	SF119668F->M82N	82	F
100	GSM119669	Superior Frontal Gyrus	Normal	SF119669F->M73N	73	F
101	GSM119670	Superior Frontal Gyrus	Normal	SF119670F->M102N	102	F
102	GSM119671	Superior Frontal Gyrus	Normal	SF119671M63N	63	M
103	GSM119672	Superior Frontal Gyrus	Normal	SF119672M->F79N	79	M
104	GSM119673	Superior Frontal Gyrus	Normal	SF119673M->F76N	76	M
105	GSM119674	Superior Frontal Gyrus	Normal	SF119674M->F83N	83	M
106	GSM119675	Superior Frontal Gyrus	Normal	SF119675M69N	69	M
107	GSM119676	Superior Frontal Gyrus	Normal	SF119676M78N	78	M
108	GSM238842	Superior Frontal Gyrus	Alzheimer's	SF238842F73A	73	F
109	GSM238843	Superior Frontal Gyrus	Alzheimer's	SF238843M81A	81	M
110	GSM238844	Superior Frontal Gyrus	Alzheimer's	SF238844M72A	72	M
111	GSM238845	Superior Frontal Gyrus	Alzheimer's	SF238845M75A	75	M
112	GSM238846	Superior Frontal Gyrus	Alzheimer's	SF238846M78A	78	M
113	GSM238847	Superior Frontal Gyrus	Alzheimer's	SF238847M75A	75	M
114	GSM238848	Superior Frontal Gyrus	Alzheimer's	SF238848M87A	87	M
115	GSM238851	Superior Frontal Gyrus	Alzheimer's	SF238851F95A	95	F
116	GSM238854	Superior Frontal Gyrus	Alzheimer's	SF238854M68A	68	M
117	GSM238855	Superior Frontal Gyrus	Alzheimer's	SF238855F95A	95	F
118	GSM238856	Superior Frontal Gyrus	Alzheimer's	SF238856F70A	70	F
119	GSM238857	Superior Frontal Gyrus	Alzheimer's	SF238857F85A	85	F
120	GSM238858	Superior Frontal Gyrus	Alzheimer's	SF238858F83A	83	F
121	GSM238860	Superior Frontal Gyrus	Alzheimer's	SF238860F77A	77	F
122	GSM238861	Superior Frontal Gyrus	Alzheimer's	SF238861F83A	83	F
123	GSM238862	Superior Frontal Gyrus	Alzheimer's	SF238862M68A	68	M
124	GSM238863	Superior Frontal Gyrus	Alzheimer's	SF238863M79A	79	M
125	GSM238864	Superior Frontal Gyrus	Alzheimer's	SF238864F82A	82	F
126	GSM238865	Superior Frontal Gyrus	Alzheimer's	SF238865M88A	88	M
127	GSM238867	Superior Frontal Gyrus	Alzheimer's	SF238867F80A	80	F
128	GSM238868	Superior Frontal Gyrus	Alzheimer's	SF238868M74A	74	M
129	GSM238870	Superior Frontal Gyrus	Alzheimer's	SF238870M72A	72	M
130	GSM238871	Superior Frontal Gyrus	Alzheimer's	SF238871M80A	80	M
131	GSM119677	Primary Visual Cortex	Normal	V119677M85N	85	M
132	GSM119678	Primary Visual Cortex	Normal	V119678M80N	80	M
133	GSM119679	Primary Visual Cortex	Normal	V119679M63N	63	M
134	GSM119680	Primary Visual Cortex	Normal	V119680M79N	79	M
135	GSM119681	Primary Visual Cortex	Normal	V119681M76N	76	M
136	GSM119682	Primary Visual Cortex	Normal	V119682M83N	83	M
137	GSM119683	Primary Visual Cortex	Normal	V119683M79N	79	M
138	GSM119684	Primary Visual Cortex	Normal	V119684F88N	88	F
139	GSM119685	Primary Visual Cortex	Normal	V119685F82N	82	F
140	GSM119686	Primary Visual Cortex	Normal	V119686F73N	73	F
141	GSM119687	Primary Visual Cortex	Normal	V119687M69N	69	M
142	GSM119688	Primary Visual Cortex	Normal	V119688M78N	78	M
143	GSM238872	Primary Visual Cortex	Alzheimer's	V238872F73A	73	F
144	GSM238873	Primary Visual Cortex	Alzheimer's	V238873M81A	81	M
145	GSM238874	Primary Visual Cortex	Alzheimer's	V238874M75A	75	M
146	GSM238875	Primary Visual Cortex	Alzheimer's	V238875M78A	78	M
147	GSM238877	Primary Visual Cortex	Alzheimer's	V238877M75A	75	M
148	GSM238941	Primary Visual Cortex	Alzheimer's	V238941M87A	87	M
149	GSM238942	Primary Visual Cortex	Alzheimer's	V238942F95A	95	F
150	GSM238943	Primary Visual Cortex	Alzheimer's	V238943M68A	68	M
151	GSM238944	Primary Visual Cortex	Alzheimer's	V238944F70A	70	F
152	GSM238945	Primary Visual Cortex	Alzheimer's	V238945F81A	81	F
153	GSM238946	Primary Visual Cortex	Alzheimer's	V238946F85A	85	F
154	GSM238947	Primary Visual Cortex	Alzheimer's	V238947M68A	68	M
155	GSM238948	Primary Visual Cortex	Alzheimer's	V238948M79A	79	M
156	GSM238949	Primary Visual Cortex	Alzheimer's	V238949F82A	82	F
157	GSM238951	Primary Visual Cortex	Alzheimer's	V238951M88A	88	M
158	GSM238952	Primary Visual Cortex	Alzheimer's	V238952M74A	74	M
159	GSM238953	Primary Visual Cortex	Alzheimer's	V238953M72A	72	M
160	GSM238955	Primary Visual Cortex	Alzheimer's	V238955M->F68A	68	M
161	GSM238963	Primary Visual Cortex	Alzheimer's	V238963F80A	80	F

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